Robert “Bobby” Gomez first visited Dr. Alex Jimenez, doctor of chiropractic, after experiencing back pain due to a pelvic tilt on his hips. Born with cerebral palsy, Bobby always felt underestimated by his peers due to his condition. Thanks to chiropractic care, Robert Gomez received the support he needed to strengthen his body as well as to improve his flexibility and mobility. Bobby describes how he received more help than he expected with Dr. Alex Jimenez.
Rehabilitation For Cerebral Palsy
Cerebral palsy is a disorder of motion, muscular tone or posture that’s brought on by brain damage that happens before birth. The impact on functional abilities with cerebral palsy varies. Generally, cerebral palsy causes movement problems with reflexes or rigidity of the limbs and back posture, and unsteady walking. People with cerebral palsy may suffer a reduced range of movement in different areas of their body. The disability associated with cerebral palsy may be limited primarily to one limb or one side of the body, or it may affect the whole body.
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Sinding-Larsen-Johansson, or SLJ, syndrome is a debilitating knee condition that most commonly affects teens during periods of rapid growth. The kneecap, or patella, is attached to the shinbone, or tibia, from the patellar tendon. The tendon connects to an expansion plate at the bottom of the kneecap throughout growth.
Repetitive stress on the patellar tendon can make the growth plate within the knee become inflamed and irritated. SLJ mainly develops in children and adolescents between the ages of 10 and 15 because that is when most people experience growth spurts. SLJ is most common in young athletes due to excess or repetitive strain in the knee.
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Causes of SLJ Syndrome
The large muscle group at the front of the upper leg is known as the quadriceps. When straightening the leg, the quadriceps pull to deliver the leg forward. This puts pressure on the growth plate at the bottom of the kneecap. During rapid growth, the bones and muscles don’t always grow at precisely the same rate.
Since the bones grow, tendons and muscles can get tight and stretched. This increases the strain around the patellar tendon and also on the growth plate it’s attached to. Repetitive or extra stress and pressure in this area can cause the growth plate to become irritated and painful. Matters that can contribute to growing SLJ syndrome are comprised of:
Sports that involve a lot of running and jumping, such as field and track or other sports such as football, gymnastics, basketball, lacrosse, and field hockey, can place stress on the knees.
Increased or incorrect physical activity can add strain on the knees. Improper form while training, shoes that don’t support the toes or an unusual way of jogging can increase chances of SLJ syndrome.
Tight or stiff quadriceps muscles can also lead to SLJ syndrome. Muscles that are more powerful and more elastic will work better, reducing the strain on the patellar and kneecap tendon.
Activities that place more pressure on the knees or demanding tasks for the knees, such as lifting heavy items, walking up and down stairs, and squatting can cause SLJ syndrome. If there’s already pain on the knee, then these movements may make it worse.
Symptoms of SLJ Syndrome
Symptoms demonstrating the presence of�Sinding-Larsen-Johansson, or SLJ, syndrome include: pain at the front of the knee or near the bottom of the kneecap, as this is the main symptom of SLJ; swelling and tenderness around the kneecap; pain that increases with physical activities like jogging, climbing stairs, or leaping; pain that becomes more acute when kneeling or squatting; and a swollen or bony bump at the bottom of the kneecap.
Sinding-Larsen-Johansson, or SLJ, syndrome is medically referred to as a juvenile osteochondrosis which affects the patella tendon in the kneecap which attaches to the inferior pole of the patella in the shinbone. Commonly characterized by knee pain and inflammation, SLJ is considered an overuse knee injury rather than a traumatic injury. Sinding-Larsen-Johansson syndrome is similar to Osgood-Schlatter syndrome.
Dr. Alex Jimenez D.C., C.C.S.T. Insight
Diagnosis of SLJ
Should you see a healthcare professional for knee problems, they will generally ask questions about how much pain the patient is experiencing and if they do any sports or other physical activities and exercises. Whether or not the patient has also had a recent growth spurt, the doctor will examine the patient’s knee for swelling and tenderness.
In very rare instances, the healthcare professional may also ask patients to acquire an X-ray or other imaging diagnostics, such as magnetic resonance imaging, or MRI, to rule out other health issues like fracture or disease.
Prevention of SLJ
The most significant way that patients can prevent getting SLJ is to stop doing physical activities which cause pain in the knee. The patient should limit themselves before the pain goes off.
It is crucial to warm up well and stretch before exercising, playing sports or engaging in any other physical activities. A jog around the track for a couple of minutes and some dynamic stretching is enough to warm up the body.
If the quadriceps muscles are tight, then you might want to do some specialized exercise and physical activity routines. Talk to your healthcare professional, such as a chiropractor or physical therapist, to discuss what’s best for you. Doing a few stretches and warm up exercises after sports or physical activities can help prevent SLJ syndrome from developing.
Treatment of SLJ
The first and most important way to treat SLJ is to stop any action that causes irritation in the knee. It’s essential for a patient to not resume any physical activities without first being cleared by a healthcare professional.
SLJ can be challenging to treat since it may not completely resolve before the bones have completely matured and the growth plates are completely shut. During physical activities, knee pain may come and go in the meantime. Other treatments to help ease SLJ syndrome include:
Use the RICE formula.
Rest. Limit physical activities as much as possible and keep weight off the knee. Walking must be kept to a minimum.
Ice. Apply ice or a cold compress to the affected area for 15 to 20 minutes every few hours. Repeat this for 2 to 3 days or until the painful symptoms have decreased.
Compress. Give the knee additional support with a strap, a band, or a ribbon. This will also�help manage symptoms.
Elevate. Keep the knee higher than the heart to reduce swelling.
Take anti-inflammatory or painkilling drugs. Painkillers like acetaminophen and ibuprofen can help relieve pain and decrease swelling.
Begin a stretching and strengthening program. After the pain and tenderness on your knee have been gone, speak with your physician or sports injury professional about a physical rehabilitation program to strengthen the muscles of your leg and increase their flexibility and range of movement.
It’s easy to become impatient when sidelined by an injury, but the proper treatment can help build the strength needed for future physical activities.�The scope of our information is limited to chiropractic as well as to spinal injuries and conditions. To discuss the subject matter, please feel free to ask Dr. Jimenez or contact us at�915-850-0900�.
Curated by Dr. Alex Jimenez
Additional Topic Discussion: Relieving Knee Pain without Surgery
Knee pain is a well-known symptom which can occur due to a variety of knee injuries and/or conditions, including sports injuries. The knee is one of the most complex joints in the human body as it is made-up of the intersection of four bones, four ligaments, various tendons, two menisci, and cartilage. According to the American Academy of Family Physicians, the most common causes of knee pain include patellar subluxation, patellar tendinitis or jumper’s knee, and Osgood-Schlatter disease. Although knee pain is most likely to occur in people over 60 years old, knee pain can also occur in children and adolescents. Knee pain can be treated at home following the RICE methods, however, severe knee injuries may require immediate medical attention, including chiropractic care.
aka Spondylodiscitis and vertebral osteomyelitis overall are relatively infrequent and may present with bimodal distribution: children and adults >50’s
Occasionally considered as two separate entities due to variations in the blood supply of pediatric vs. adult spines
Risk factors/causes: distant site of infection in the body (25-35%), e.g., oropharynx, urogenital infections, bacterial endocarditis, indwelling catheters, florid skin infections furunculosis/abscess, etc.
Iatrogenic:�operative (e.g., discectomy) interventional or diagnostic/therapeutic procedures
Penetrating trauma
Immunocompromised patients
Diabetics
Malnourished patients or patients with low protein
IV drug users
Chronic disease patients, cancer patients etc.
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Potential Pathological Sequence
Clinical Presentation
Back pain with or w/o high fever and other “septic” signs. Fever may only present in 50% of children
Exacerbation of pre-existing back pain in post-surgical cases
Neurological complications in advanced cases of vertebral destruction and epidural abscess
Meningitis, septicemia etc.
Labs: Blood tests are unspecific, may or may not indicate elevated ESR/CRP, WBC
Diagnostic imaging is important but
If clinical suspicion is strong, prompt I.V. antibiotics are needed to prevent serious complications
Routes of Infection
Infection routes to the spine are similar to bone in general
3-distinct routes:
1) Hematogenous spread as bacteremia (most common)
2) Adjacent site of infection (e.g., soft tissue abscess)
3)Direct inoculation (e.g., iatrogenic or traumatic)
M/C organism Staph. Aureus
Mycobacterium TB (tuberculous spinal osteomyelitis) aka Pott’s disease can be presented in cases of re-activated or disseminated pulmonary TB
Mechanisms of Spinal Infection
May vary depending on the patients’ age
In children, the IVD receives direct blood supply and can be infected directly spreading to adjacent bone and causing spondylodiscitis
In Adults
The disc is avascular
Pathogens invade adjacent vertebral end-plates via end-arterial supply of the vertebral body that may facilitate infection due to slow, turbulent flow
Organisms may then quickly gain access to disc substance rich in nutrients (discitis) often w/o significant initially visible destruction to the bone
Thus, one of the earliest rad. findings of spinal infection or sudden reduction of disc height
Later end-plate irregularity/sclerosis may develop, subsequently affecting the entire adjacent vertebral bodies
Diagnostic Imaging
Initially, in most cases of MSK complaints, radiography is the 1st imaging step
Initially, X-radiography is often unrewarding and may appear unremarkable for 7-10 days or presents with some subtle soft tissue changes (e.g., obscuration of Psoas shadows etc.)
Some of the earliest x-ray signs of pyogenic spondylodiscitis: sudden reduction of disc height (above arrow) during initial 7-10 days
Subsequently (10-20 days) some end-plate irregularity and adjacent sclerosis may be noted
In more advanced cases, subsequent vertebral destruction and collapse may occur
N.B. Reliable feature to DDx between spinal infection and metastasis is the preservation of disc height in the latter
Note:�sudden disc narrowing with no appreciable spondylosis (above the first image) is suspicious for infection (discitis)
MRI +C is required to evaluate suspected infection
N.B. 50-60% of pyogenic spondylodiscitis occur in the lumbar region
AP & Lateral Lumbar Radiographs
Note severe disc narrowing and adjacent vertebral body destruction at L1-L2 in a 68 -y.o.-female with a known Hx of type 2 DM
Additional imaging modalities should be used to support the Dx
Final Dx: Pyogenic Spondylodiscitis
Sagittal T1 & T2 MRI
Weighted MRI slices of a patient who had laminectomy at L4
MR imaging with gad contrast is the modality of choice for Dx of spinal infection
Early septic changes affecting the disc and adjacent vertebral end-plates are readily demonstrated as a low signal on T1 and high T2/STIR d/t edema and inflammation
T1 FS +C gad images show avid enhancement of the lesion due to granulation tissue around the phlegmon. Peripheral enhancement is also characteristic of an abscess.
Epidural extension/abscess can also be successfully detected my MRI
N.B. 50% of epidural abscess cases present with neurological signs
STIR & T1 FS +C Gad Sagittal MRI
Marked septic collection and edema affecting L4-5 disc and vertebral body with some epidural extension and paraspinal soft tissue edema. Avid contrast enhancement is noted surrounding low signal foci within the bone and disc tissue, some gad. Enhancement is noted in posterior paraspinal muscles and dural spaces
Management: Dx of spondylodiscitis requires prompt I.V antibiotics. If instability and neurological complications develop referral to a Neurosurgeon is required
MRI Unavailable or Contraindicated
Bone scintigraphy is very sensitive but non-specific for spinal infection but overall is of great value d/t higher sensitivity than x-rays and relatively low cost.
An area of increased flow with radiopharmaceutical uptake is characteristic but not specific sign of spondylodiscitis
If neurological signs are present and MRI is contraindicated than CT myelography may be used
TB Osteomyelitis aka Pott’s Disease
TB osteomyelitis is increasing d/t HIV and other immunocompromised states. Extrapulmonary TB m/c affects the spine and especially the thoracic spine (60%)
Radiographic Pathology:�TB bacillus infects the vertebral body and often spreads subligamentously. “Cold” paraspinal abscess collection may develop and spreads along fascial planes, e.g., Psoas abscess. Disc spaces are preserved until v. late and skip areas are noted helping to DDx TB from pyogenic infection. Severe vertebral destruction aka Gibbus deformity may develop (>60-degree sometimes) and may become permanent. Neurologic and many regional complications may develop
Imagingapproach:�CXR with spinal x-rays 1st step that may be unrewarding but may potentially reveal VB destruction w/o disc narrowing. CT scanning is more superior than x-rays. MRI with gad C is a modality of choice
Patellar tendinitis is a common health issue characterized by the inflammation of the tendon which joins the kneecap, or patella, to the shinbone, or tibia. The knee pain associated with this problem may range from mild to severe depending on the circumstances of the knee injury.
Patellar tendinitis, or jumper’s knee, is a well-known sports injury among athletes who play in basketball and volleyball. Among recreational volleyball players, an estimated 14.4 percent of them have jumper’s knee, where the incidence is even higher for professional athletes. An estimated 40 to 50 percent of elite volleyball players have patellar tendinitis.
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Causes of Patellar Tendinitis
Patellar tendinitis is caused by repetitive strain on the knee, most often from overuse in physical activities. Stress can create tears along the tendons which can cause inflammation in the complex structures of the knee.
Other contributing factors of patellar tendinitis include:
Tight or stiff leg muscles
Uneven leg muscle strength
Misaligned toes, ankles, and legs
Obesity
Sneakers without enough padding
Tough playing surfaces
Chronic health issues that weaken the tendon
Athletes have a higher chance of developing patellar tendinitis because running, jumping, and squatting put more force over the tendon. Running can place a force of as many as five times the body weight on the knees.
Intense physical activity for an extended amount of time has been previously associated with jumper’s knee. A 2014 research study noted that jump frequency was also a significant risk factor for amateur players.
Symptoms of Patellar Tendinitis
The initial symptoms of patellar tendinitis include pain,�discomfort, and tenderness at the base of the kneecap or patella. Other symptoms of patellar tendinitis may include a burning sensation. For many patients, getting up from a squat or kneeling down can also be particularly debilitating.
The pain associated with patellar tendinitis may be irregular at first, manifesting immediately after participating in physical activities. Damage or injury to the tendon can also make the pain worse. Jumper’s knee can affect regular daily activities, such as climbing stairs or sitting in a vehicle.
�
Patellar tendinitis, also known as “jumper’s knee”, is a particularly common cause of pain and discomfort in the patellar region of many athletes. While it frequently occurs as a result of repetitive or continuous jumping, research studies have demonstrated that patellar tendinitis may be associated with stiff ankle movements and ankle sprains, among other sports injuries.
Dr. Alex Jimenez D.C., C.C.S.T. Insight
Patellar Tendinitis Diagnosis
At the start of a�consultation, the healthcare professional will first ask the patient about their specific health issue. The doctor will then physically evaluate the patient’s knee, probe for where they are feeling pain, and test the assortment of knee motion by bending and extending the patient’s leg.
Furthermore, the healthcare professional may additionally order imaging diagnostics to find out if there’s any damage or injury to the tendon or even the bone. These tests can help rule out a broken bone, or fracture. The doctor may use an X-ray to look for a displaced or fractured kneecap, and an MRI or an ultrasound to reveal any harm to the soft tissue.
Patellar Tendinitis Treatment
Treatment for patellar tendinitis depends on the damage or injury to the knee. Conservative steps to reduce pain, such as rest or exercises are generally the first line of treatment. The healthcare professional will usually recommend a span of controlled rest, where they will prevent the patient from engaging in physical activities that put�pressure on the knee.
Drugs and/or Medications
The healthcare professional may prescribe over-the-counter drugs and/or medications for short-term pain relief and inflammation reduction.
These can consist of:
Ibuprofen (Advil)
Naproxen sodium (Aleve)
cetaminophen (Tylenol)
If the patient’s symptoms are severe, the healthcare professional may recommend the use of corticosteroid injection in the area around the patellar tendon. This treatment is effective in reducing acute pain.
Another method of utilizing corticosteroid for patellar tendinitis is by spreading the medication over the affected knee and use a low electrical charge to push it through the skin, in a process known as iontophoresis.
Chiropractic Care and Physical Therapy
The goal of chiropractic care and physical therapy for patellar tendinitis is to reduce pain and inflammation, among other symptoms, as well as to strengthen the leg and thigh muscles with stretches and exercises.
If the patient’s symptoms are severe, even while resting, the doctor may recommend that you wear a brace and then use crutches to avoid additional damage or injury to the tendon. If the patient has no painful symptoms, then they can start participating in a physical therapy activities.
A rehabilitation program generally consists of:
A warm-up interval
Massage, heat or ice to the�knee
Stretching exercises
Strengthening exercises
A doctor of chiropractic, or chiropractor, may use ultrasound and electrical stimulation to relieve the patient’s knee pain. A�knee brace or taping of the knee might also help reduce pain by supporting the kneecap when engaging in physical activities. The healthcare professional may develop a workout program that may include a series of stretches and exercises.
Surgery
When other treatments are not effective in relieving painful symptoms associated with patellar tendinitis, the doctor may advise surgery to repair the patellar tendon. Traditional surgery involves opening the knee to scrape on the kneecap and tendon. More recently,�arthroscopic surgery is used for this particular process. This surgical intervention involves making four small incisions in the knee and it has a shorter recovery time.
The recovery period for surgery varies per procedure. Some surgical intervention advise for immobilization with a cast. Others suggest�an immediate rehabilitation program. Regardless of the level of damage and/or injury, it’s essential for patients to seek medical attention for their patellar tendinitis. The scope of our information is limited to chiropractic as well as to spinal injuries and conditions. To discuss the subject matter, please feel free to ask Dr. Jimenez or contact us at�915-850-0900�.
Curated by Dr. Alex Jimenez
Additional Topic Discussion: Relieving Knee Pain without Surgery
Knee pain is a well-known symptom which can occur due to a variety of knee injuries and/or conditions, including sports injuries. The knee is one of the most complex joints in the human body as it is made-up of the intersection of four bones, four ligaments, various tendons, two menisci, and cartilage. According to the American Academy of Family Physicians, the most common causes of knee pain include patellar subluxation, patellar tendinitis or jumper’s knee, and Osgood-Schlatter disease. Although knee pain is most likely to occur in people over 60 years old, knee pain can also occur in children and adolescents. Knee pain can be treated at home following the RICE methods, however, severe knee injuries may require immediate medical attention, including chiropractic care.
Headaches are a real pain (insert eye-roll here). Many individuals suffer from them, and there are a variety of causes, symptoms, and treatment options. For some, they are a rare occurrence, while others deal with them weekly or even daily. They can range from minor inconveniences to full-fledged life-changing afflictions.
The first step in treating headaches is to understand the type of headache you are experiencing. Some people think they have a migraine when in fact, they are suffering from a tension headache. While tension headaches are more common, it’s estimated by the Migraine Research Foundation that 1 in 4 U.S. Households include someone with a migraine.
Determining which headache is being dealt with takes a bit of research. Individuals suffering from headaches need to ask themselves these questions to determine if they are having a migraine or experiencing a tension headache.
When in life did the headaches begin? According to the Mayo Clinic, migraines start in adolescence or early adulthood. In contrast, tension headaches can start at any time in a person’s life. If an adult just began suffering from headaches, they are most likely tension headaches.
Where does it hurt? The location of the pain is a vital indicator of the type of headache. Migraines typically occur on one side of the head. Tension headaches affect both sides of the head and can produce a feeling of pressure in the forehead area.
What kind of pain is it? If it is a dull pain, a feeling of pressure, or tenderness around the scalp, it’s most likely a tension headache. If, on the other hand, the pain is throbbing or pulsing pain, it could be a migraine. Both headaches can offer up severe pain, just different types.
Are there any other symptoms?Migraines typically come with symptoms beyond head pain. Nausea, light and sound sensitivity, bright flashing or sparkling lights, pins and needle sensations down one or both arms, or dizziness are common. Individuals who don’t experience any of these symptoms are most likely dealing with a tension headache.
Can you function? While painful and frustrating, many people with a tension headache can still perform their jobs, drive, read, and deal with daily life. A migraine is a different story. Lying in a dark, quiet room with a sleep mask on until the headache passes is how most people handle migraines. If the headache is life-disrupting, it could very well be a migraine.
Do regular painkillers work? Tension headaches can often be relieved by over-the-counter pain medications. Migraines don’t budge with these treatments. Once a migraine is in full force, the sufferer must ride it out. If a headache reacts well to a couple of non-prescription painkillers, it’s most likely a tension headache.
Most individuals will, unfortunately, deal with a headache at one point in their lives. It’s important to note that tension headaches are much more common than migraines, but that doesn’t rule out the possibility of a headache being a migraine. The answers to the above questions give insight into the type of headache occurring and how best to handle the treatment proactively. No matter the type of headache, if the pain is severe, or begins after a head injury, seek medical treatment immediately.
Ischemic Osteonecrosis (More accurate term) aka avascular necrosis AVN: this term describes subarticular (subchondral) bone death
Intramedullary bone infarct: depicts osteonecrosis within the medullary cavity of the bone (above x-ray image)
Causes: m/c: trauma, systemic corticosteroids, diabetes, vasculitis in SLE. The list is long. Other vital causes: Sickle cell disease, Gaucher disease, alcohol, caisson disease, SCFE, LCP, etc.
Pathology: ischemia and bone infarct with resultant devitalized center surrounded by ischemia and edema with normal bone on the outer periphery (MRI double line sign)
Sub-articular necrotic bone eventually collapses and fragments leading to progressive bone and cartilage destruction and rapidly progressing DJD
Early Dx often missed but crucial to prevent severe DJD
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M/C Sites
Hips, shoulders, talus, scaphoid bone. Many peripheral idiopathic AVN sites are known by their eponyms (e.g., Kienbock aka AVN of the lunate bone, Preisier aka scaphoid AVN)
Radiography is insensitive to early AVN and may only present as subtle osteopenia
Some of the early appreciable rad features are increased patchy bone sclerosis followed by sub-articular bone collapse or “crescent sign” signifying stage-3 on Ficat classification (above)
Earliest detection and early intervention can be achieved by MRI (most sensitive modality)
If MRI contraindicated or unavailable, 2nd most sensitive modality is radionuclide bone scan (scintigraphy)
X-ray and CT scanning are of equal value
Coronal MRI Slice
Fluid sensitive, sensitive coronal MRI slice revealing bill ischemic osteonecrosis of the femoral head
MRI findings: l
Tc99-MMDP Radionuclide Bone
Bone scan reveals a central area of photopenia (cold spot) d/t necrotic fragment surrounded by increased osteoblastic activity as increased uptake of Tc-99 MDP in the right hip
The patient is a 30-year-old female with breast cancer and chemotherapy treatment who suddenly presented with right hip pain
Radiographic Progression of AVN
Later stages present with articular collapse, subarticular cysts, increased patchy sclerosis and complete flattening of the femoral head with resultant severe DJD. Rx: THA
Management
Early imaging Dx with MRI or bone scintigraphy is essential
Referral to the Orthopedic surgeon
Core decompression (above) can be used to revascularize the affected bone during earlier stages but produces mixed results
Delayed changes of AVN: THA as IN severe DJD cases
B/L THA
B/L THA in the patient with ischemic osteonecrosis of the right and later left hip
When B/L hip AVN is present, typically consider systemic causes (corticosteroids, diabetes)
Inflammatory Arthritis Affecting the Hip
Consider common systemic inflammatory condition such as RA and AS/EnA
Hip RA may develop in 30% of patients with RA
Key features to DDx inflammatory arthritis vs. DJD is symmetrical/uniform aka concentric joint loss often leading to axial migration and Protrusion Acetabule in advanced cases
Key element between RA vs. AS: the presence of RA bone erosion w/o productive bone changes or enthesitis in AS d/t inflammatory subperiosteal bone proliferation, whiskering/fluffy periostitis (collar-type enthesitis circumferentially affecting head-neck junction)
Dx: Hx, PE, labs: CRP, RH, anti-CCP Ab (RA)
CRP, HLA-B27, RF- (AS)
Septic Arthritis
Gonococcal infections, iatrogenic causes, I.V. drug use, and some others
Routes:�hematogenous, adjacent spread, direct inoculation (e.g., iatrogenic)
Clinically: pain and reduced ROM presented as monoarthritis, generalized signs/symptoms. CBC, ESR, CRP changes. ARthrocentesis and culture are crucial
M/C pathogen Staph. Aureus & Neisseria Gonorrhea
1st step: radiography, often unrewarding in the early stage. Later (4-10 days) indistinctness of the white cortical line at the femoral articular epiphysis, loss of joint space, effusion as a widening of the medial joint area (Waldenstrom sign)
MRI – best at early DX: T1, T2, STIR, T1+C may help with early. Early I.V. antibiotics crucial to prevent rapid joint destruction
Slipped Capital Femoral Epiphysis (SCFE)
Important to diagnose but easily missed potentially leading to Ischemic Osteonecrosis of the femoral head aka AVN
Presents typically in overweight children (more often boys), age over eight years. Greater incidence in African-American boys
1st step: radiography, especially look for a widened physeal growth plate (so-called pre-slip). Later, slip and disturbed Klein’s line (above image). MRI – best modality for early Dx and early intervention
The frog lateral view often demonstrates the medial slip better than the AP view
Clinically Limping Child or Adolescent
M>F (10-18 years). African-Americans are at greater risk. 20% of cases of SCFE are B/L. Complications: AVN >>DJD
Radiography:�AP pelvis, spot, and frog leg may reveal slippage as Klein line failed to cross through the lateral aspect of the femoral head
Additional features: physis may appear widened
MRI w/o gad, is required for the earliest Dx and prevention of complications (AVN)
Normal and Abnormal Klein Line
Consistent with SCFE. The physis is also widened. Dx: SCFE
Urgent referral to the Pediatric Orthopedic surgeon
Subtle Changes in Left Hip
Note suspected subtle changes in the left hip that may require MR examination to confirm the Dx
Delay in care may result in major complications
Perthes’ Disease
aka Legg-Calves-Perthes Disease (LCP)
Refers to Osteochondritis of the femoral head with osteonecrosis likely d/t disturbed vascularization of the femoral head
Presents typically in children (more often boys) aged under eight years as atraumatic “limping child.” 15% may have B/L Perthe’s
Imaging steps: 1st step x-radiography, followed by MRI especially in stage 1 (early) w/o x-ray abnormalities
Unspecific signs: joint effusion with Waldenstrome sign+ (>2-mm increase in medial joint space compared to the opposite side). Past approach: Fluoroscopic Arthrography (replaced by MRI)
Pathologic-Radiologic Correlation: in well-established cases, the femoral head characteristically becomes sclerotic, flattened and fragmented due to avascular necrosis (AVN). Later on, an occasional Coxa Magna changes may develop (>10% femoral head enlargement)
Management: symptoms control, bracing. Boys at younger ate show better prognosis d/t more immaturity and better chances of bone/cartilage repair mechanisms. In advanced cases, operative care: osteotomy, hip arthroplasty in adulthood if advanced DJD develops
Common Neoplasms & Other Conditions Affecting Hip/Pelvis
M/C hip & pelvis neoplasms in adults: bone metastasis ( above far left), 2nd m/c Multiple Myeloma (M/C primary bone malignancy in adults). Tips: remember Red Marrow distribution. Less frequent: Chondrosarcoma
Paget’s disease of bone (above-bottom left image) is m/c detected in the pelvis and Femurs
Children and young adults ‘limping child’ benign neoplasms: Fibrous Dysplasia (above middle image), Solitary Bone Cyst (21%), Osteoid Osteoma, Chondroblastoma. Malignant pediatric neoplasms: m/c Ewing Sarcoma (above middle right and bottom images) vs. Osteosarcoma. >2y.o-consider Neuroblastoma
Imaging: 1st step: radiography followed by MRI are most appropriate.
If Mets are suspected: Tc99 bone scintigraphy is most sensitive
Multiple Myeloma
Multiple Myeloma in a 75-y.o male (AP pelvis view)
Chondrosarcoma in a 60-y.o male (axial and coronal reconstructed CT+C slices in the bone window)
Bisphosphonates are a type of drug/medication which blocks the loss of bone density to treat osteoporosis-related ailments. They are most frequently prescribed for the treatment of osteoporosis. Bisphosphonates have two phosphonate groups. Evidence demonstrates that they reduce the probability of fractures in post-menopausal women with osteoporosis.
Bone tissue undergoes continuous remodeling that is stored to provide equilibrium, or homeostasis, through osteoblasts generating bone and osteoclasts ruining bone. Bisphosphonates inhibit bone digestion by encouraging osteoclasts to undergo apoptosis or cell death.
The uses of bisphosphonates include the prevention and treatment of osteoporosis, Paget’s disease of bone, bone metastasis (with or without hypercalcaemia), multiple myeloma, primary hyperparathyroidism, osteogenesis imperfecta, fibrous dysplasia, and other conditions which exhibit bone fragility. The purpose of the following article is to discuss the mechanism of action and role in the clinical practice of bisphosphonates.
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Abstract
Bisphosphonates are primary agents in the current pharmacological arsenal against osteoclast-mediated bone loss due to osteoporosis, Paget disease of bone, malignancies metastatic to bone, multiple myeloma, and hypercalcemia of malignancy. In addition to currently approved uses, bisphosphonates are commonly prescribed for prevention and treatment of a variety of other skeletal conditions, such as low bone density and osteogenesis imperfecta. However, the recent recognition that bisphosphonate use is associated with pathologic conditions including osteonecrosis of the jaw has sharpened the level of scrutiny of the current widespread use of bisphosphonate therapy. Using the key words bisphosphonate and clinical practice in a PubMed literature search from January 1, 1998, to May 1, 2008, we review current understanding of the mechanisms by which bisphosphonates exert their effects on osteoclasts, discuss the role of bisphosphonates in clinical practice, and highlight some areas of concern associated with bisphosphonate use.
Introduction
Since their introduction to clinical practice more than 3 decades ago, bisphosphonates have been increasingly used for an array of skeletal disorders. Bisphosphonates are now used to treat such varied conditions as heritable skeletal disorders in children, postmenopausal and glucocorticoid-induced osteoporosis (GIO), and bone metastases in patients with malignancies. Bisphosphonates can offer substantial clinical benefit in conditions in which an imbalance between osteoblast-mediated bone formation and osteoclast-mediated bone resorption underlies disease pathology; however, the more recently recognized association of bisphosphonate use with pathologic conditions, including low bone turnover states with resultant pathologic fractures, osteonecrosis of the jaw (ONJ), and an increased incidence of atrial fibrillation, has brought increased scrutiny to the current broad use of bisphosphonate therapy.
PubMed literature from January 1, 1998, to May 1, 2008, was reviewed using bisphosphonate and clinical practice as search terms. Additional articles not obtained in the primary search were identified by assessment of literature referenced in the reviewed articles. We present data on the development of bisphosphonates as therapeutic agents, the proposed mechanisms by which these agents exert their effects, and the current roles for bisphosphonate therapy in clinical practice. Additionally, we address some areas of concern for clinicians and draw attention to some currently unresolved issues associated with bisphosphonate use.
Chemical Structure as Basis for Clinical Activity
Structurally, bisphosphonates are chemically stable derivatives of inorganic pyrophosphate (PPi), a naturally occurring compound in which 2 phosphate groups are linked by esterification (Figure 1, A). Within humans, PPi is released as a by-product of many of the body�s synthetic reactions; thus, it can be readily detected in many tissues, including blood and urine.1 Pioneering studies from the 1960s demonstrated that PPi was capable of inhibiting calcification by binding to hydroxyapatite crystals, leading to the hypothesis that regulation of PPi levels could be the mechanism by which bone mineralization is regulated.2
Like their natural analogue PPi, bisphosphonates have a very high affinity for bone mineral because they bind to hydroxyapatite crystals. Accordingly, bisphosphonate skeletal retention depends on availability of hydroxyapatite binding sites. Bisphosphonates are preferentially incorporated into sites of active bone remodeling, as commonly occurs in conditions characterized by accelerated skeletal turnover. Bisphosphonate not retained in the skeleton is rapidly cleared from the circulation by renal excretion. In addition to their ability to inhibit calcification, bisphosphonates inhibit hydroxyapatite breakdown, thereby effectively suppressing bone resorption.3 This fundamental property of bisphosphonates has led to their utility as clinical agents. More recently, it has been suggested that bisphosphonates also function to limit both osteoblast and osteocyte apoptosis.4,5 The relative importance of this function for bisphosphonate activity is currently unclear.
Modification of the chemical structure of bisphosphonates has widened the differences between the effective bisphosphonate concentrations needed for antiresorptive activity relative to those that inhibit bone matrix mineralization, making the circulating concentrations of all bisphosphonates currently used in clinical practice active essentially only for the inhibition of skeletal resorption.1 As shown in Figure 1, A, the core structure of bisphosphonates differs only slightly from PPi in that bisphosphonates contain a central nonhydrolyzable carbon; the phosphate groups flanking this central carbon are maintained. As detailed in Figure 1, B, and distinct from PPi, nearly all bisphosphonates in current clinical use also have a hydroxyl group attached to the central carbon (termed the R1 position). The flanking phosphate groups provide bisphosphonates with a strong affinity for hydroxyapatite crystals in bone (and are also seen in PPi), whereas the hydroxyl motif further increases a bisphosphonate�s ability to bind calcium. Collectively, the phosphate and hydroxyl groups create a tertiary rather than a binary interaction between the bisphosphonate and the bone matrix, giving bisphosphonates their remarkable specificity for bone.1
Although the phosphate and hydroxyl groups are essential for bisphosphonate affinity for bone matrix, the final structural moiety (in the R2 position) bound to the central carbon is the primary determinant of a bisphosphonate�s potency for inhibition of bone resorption. The presence of a nitrogen or amino group increases the bisphosphonate�s antiresorptive potency by 10 to 10,000 relative to early non�nitrogen-containing bisphosphonates, such as etidronate.1,6 Recent studies (described subsequently) delineate the molecular mechanism by which nitrogen-containing bisphosphonates inhibit osteoclast activity.
A critical pharmacological feature of all bisphosphonates is their extremely high affinity for, and consequent deposition into, bone relative to other tissues. This high affinity for bone mineral allows bisphosphonates to achieve a high local concentration throughout the entire skeleton. Accordingly, bisphosphonates have become the primary therapy for skeletal disorders characterized by excessive or imbalanced skeletal remodeling, in which osteoclast and osteoblast activities are not tightly coupled, leading to excessive osteoclast-mediated bone resorption.
Early non�nitrogen-containing bisphosphonates (etidronate, clodronate, and tiludronate) (Figure 1, B) are considered first-generation bisphosphonates. Because of their close structural similarity to PPi, non�nitrogen-containing bisphosphonates become incorporated into molecules of newly formed adenosine triphosphate (ATP) by the class II aminoacyl�transfer RNA synthetases after osteoclast-mediated uptake from the bone mineral surface.1 Intracellular accumulation of these nonhydrolyzable ATP analogues is believed to be cytotoxic to osteoclasts because they inhibit multiple ATP-dependent cellular processes, leading to osteoclast apoptosis.
Unlike early bisphosphonates, second- and third-generation bisphosphonates (alendronate, risedronate, ibandronate, pamidronate, and zoledronic acid) have nitrogen-containing R2 side chains (Figure 1, C). The mechanism by which nitrogen-containing bisphosphonates promote osteoclast apoptosis is distinct from that of the non�nitrogen-containing bisphosphonates. As elegantly illustrated in recent studies, nitrogen-containing bisphosphonates bind to and inhibit the activity of farnesyl pyrophosphate synthase, a key regulatory enzyme in the mevalonic acid pathway critical to the production of cholesterol, other sterols, and isoprenoid lipids6,7 (Figure 2, A). the analog is likely a direct function of the ability of bisphosphonates to selectively adhere to and be retained within bone before endocytosis within osteoclasts during osteoclast-mediated bone mineral dissolution and matrix digestion (Figure 2, B). Given the fact that nearly all patients now receive treatment with the more potent nitrogen-containing bisphosphonates rather than the earlier non�nitrogen-containing bisphosphonates, the remainder of this review focuses on this more recent class of bisphosphonates.
Additional Clinical Features
Although bisphosphonate-mediated induction of osteoclast apoptosis cannot be measured directly within the clinical setting, a temporal reduction in biochemical markers of bone resorption (namely amino- and carboxyl-terminal breakdown products of type 1 collagen in serum and urine) after bisphosphonate initiation is considered a reasonably reliable surrogate of bisphosphonate efficacy and potency. Maximum suppression of bone resorption occurs within approximately 3 months of initiation of oral bisphosphonate therapy given daily, weekly, or monthly and remains roughly constant with continuation of treatment.10�12 Resorption is suppressed more rapidly after intravenous (IV) bisphosphonate administration than after oral bisphosphonate therapy.
As might be anticipated, length of suppression is largely a function of bisphosphonate potency for mineral matrix binding, such that the most potent bisphosphonate, zoledronic acid, at a dose of either 4 mg13 or 5 mg (the dose approved by the Food and Drug Administration [FDA] for osteoporosis),14 effectively suppresses biochemical markers of bone resorption for up to 1 year in women with postmenopausal osteoporosis. Although the precise biologic half-lives of the currently used nitrogen-containing bisphosphonates remain the subject of debate largely because of technical challenges required to determine bisphosphonate levels in urine and serum, estimates for the potent bisphosphonate alendronate suggest a biologic half-life of more than 10 years after single-dose IV administration.15
A critical feature governing the clinical pharmacology of bisphosphonates is their bioavailability. As a class, bisphosphonates are very hydrophilic. Accordingly, they are poorly absorbed from the gastrointestinal tract after oral administration (generally with absorption of <1% for an oral dose), instead undergoing paracellular transport because they are not lipophilic.16 Further, only about 50% of the absorbed drug is selectively retained in the skeleton, whereas the remainder is eliminated in the urine without being metabolized. Skeletal uptake and retention are primarily dependent on host factors (renal function, prevalent rate of bone turnover, and binding site availability) and bisphosphonate potency for bone matrix.12 The amount of bisphosphonate retained after either oral or IV administration varies widely both between patients and across clinical conditions and is primarily believed to reflect variations in bone turnover.12
A previous impediment for many patients prescribed oral bisphosphonate therapy was the inconvenience associated with daily oral administration (requiring patients to remain upright for 30 minutes and refrain from eating any food both 2 hours before and at least 30 minutes after pill ingestion) and the relatively common association with gastrointestinal symptoms. The more recent development of pharmacologically equivalent preparations allowing for once-weekly (alendronate or risedronate) or even monthly (ibandronate or risedronate) oral administration has profoundly affected bisphosphonate delivery for most patients for whom convenience (and thus adherence to therapy) was an issue and has correspondingly lead to higher rates of adherence.17,18 Further, the availability of IV preparations (pamidronate, ibandronate, and zoledronic acid), which for most clinical conditions require even less frequent dosing, has eliminated the gastrointestinal adverse effects incurred by some patients managed with oral bisphosphonates, although the rate of acute phase reactions characterized by flulike symptoms (low-grade fever, myalgias and arthralgias, or headache) is increased in patients receiving IV rather than oral bisphosphonate treatment.14
Role in Clinical Practice
As aforementioned, bisphosphonates promote the apoptosis of osteoclasts actively engaged in the degradation of mineral on the bone surface. Accordingly, bisphosphonates have become the primary therapy for managing skeletal conditions characterized by increased osteoclast-mediated bone resorption. Such excessive resorption underlies several pathologic conditions for which bisphosphonates are now commonly used, including multiple forms of osteoporosis (juvenile, postmenopausal or involutional [senile], glucocorticoid-induced, transplant-induced, immobility-induced, and androgen-deprivation�related), Paget disease of bone, osteogenesis imperfecta (OI), hypercalcemia, and malignancy metastatic to bone.
Although each of the nitrogen-containing bisphosphonates is more potent than the non�nitrogen-containing bisphosphonates, their ability to suppress osteoclast activity (as measured by biochemical markers of bone turnover) varies. However, whether superior suppression of bone turnover is relevant for fracture prevention remains to be determined. Indeed, data suggest that adherence to long-term bisphosphonate therapy, rather than the specific bisphosphonate used, is the most important factor in determining the effectiveness of treatment for limiting fracture risk.19,20 Accordingly, studies examining bisphosphonate therapy adherence suggest that, by addressing patient concerns of medication safety and timing, clinicians can significantly improve adherence.21 Whether weekly or monthly oral bisphosphonate dosing leads to higher rates of adherence to therapy is currently unknown.
Osteoporosis
The most common clinical condition for which bisphosphonate therapy is used is osteoporosis, a skeletal condition characterized by compromised bone strength resulting in an increased risk of fracture. As previously noted, osteoporosis is a clinically heterogeneous disease with a range of origins, including hormone loss (postmenopausal and androgen-deprivation), iatrogenic (glucocorticoid-induced and transplant-related), physical (immobility), and genetic (eg, juvenile and OI-associated). Often these conditions overlap within individual patients.
Postmenopausal osteoporosis is characterized by an imbalance between osteoclast-mediated bone resorption and osteoblast-mediated bone formation such that bone resorption is increased. This relative imbalance leads to diminution of skeletal mass, deterioration of bone microarchitecture, and increased fracture risk. During the past 2 decades, bisphosphonate therapy has become the leading clinical intervention for postmenopausal osteoporosis because of the ability of bisphosphonates to selectively suppress osteoclast activity and thereby retard bone resorption. The fracture reduction and concomitant increases in bone density generally seen with bisphosphonate use are believed to result from a decline in the activation frequency of new remodeling units formed by osteoclasts, with relative preservation (at least initially) of osteoblast activity. As such, the initial stabilization and retention of trabecular connectivity allow the duration of secondary mineral deposition on the structural scaffold to be prolonged, thereby increasing the percentage of bone structural units that reach a maximum degree of mineralization.22 This increase in the mean degree of skeletal mineralization underlies both improvements in bone density and reductions in fracture risk after bisphosphonate therapy.
Importantly, this role for bisphosphonates was indirectly buttressed by the early termination of the estrogen and progesterone arm of the Women�s Health Initiative (WHI), because of concern about increased rates of coronary artery disease and breast cancer among women receiving hormonal therapy. For most practitioners and patients, the WHI results effectively limited the practice of treating postmenopausal osteoporosis with hormone replacement therapy, despite the strong evidence provided in the WHI and previous studies that estrogen is highly effective in preventing fractures.23
Among the oral bisphosphonates, both alendronate and risedronate have been conclusively demonstrated to reduce the number of vertebral24�26 and hip fractures,24,27 progression of vertebral deformities, and height loss in postmenopausal women with osteoporosis.28 Ibandronate, developed more recently and available in both oral and IV preparations, has been demonstrated to reduce only the risk of vertebral fracture,29,30 although the sample size estimates used did not allow sufficient power to detect an effect on nonvertebral or hip fractures. The relative fracture risk reduction in vertebral, hip, and nonvertebral sites in post-menopausal women with known osteoporosis after 3 years of bisphosphonate treatment is compared in the Table.
Reductions in fracture incidence occur before demonstrable changes (measured by dual-energy x-ray absorptiometry [DXA]) in bone mineral density (BMD), suggesting that stabilization of existing skeletal microarchitecture or decreased bone turnover is sufficient for fracture risk reduction.31 Daily alendronate use at doses of 10 mg for up to 10 years was well tolerated and was not associated with adverse skeletal outcomes.32 Whereas nearly all osteoporosis trials in which bisphosphonate therapy has been used involved postmenopausal women, general trials that have examined men with a diagnosis of either low bone mass or osteoporosis have demonstrated similar responses to bisphosphonate therapy.33�35
In the Fracture Intervention Trial Long-term Extension, postmenopausal women with low femoral neck BMD (but not necessarily with DXA-defined osteoporosis) were treated with daily alendronate for 5 years and then randomized to receive either alendronate or placebo for an additional 5 years. Women who discontinued alendronate therapy had statistically significant, although clinically relatively small, declines in BMD and associated increases in biochemical markers of bone turnover compared with women who continued therapy.36 Importantly, no significant differences were found for either nonvertebral fractures or all clinical fractures; however, there was a slightly higher (and statistically significant) risk of clinical vertebral fractures in the placebo group (absolute risk, 2.9%), but this was not a primary or secondary study end point. Formal studies of alendronate cessation with more statistical power for fracture assessment after discontinuation as a primary end point or of other bisphosphonates have not yet established that, for at least some patients with postmenopausal osteoporosis, a drug holiday could be reasonable after a period of bisphosphonate therapy.
Initial studies used daily bisphosphonate dosing; more recent studies have focused on weekly (alendronate and risedronate) or monthly (ibandronate, and more recently risedronate37) dosing, regimens believed to have pharmacodynamic equivalence to daily dosing of each drug. However, all studies to date using intermittent weekly or monthly oral bisphosphonate therapy have relied on surrogate markers, such as biochemical markers of bone resorption or changes in BMD measured by DXA, rather than primary fracture outcomes, for determination of efficacy. In contrast, the BONE trial, in which oral ibandronate was administered every other day for 12 doses every 3 months, did reduce vertebral fractures with intermittent dosing,30 although this dosing regimen is not approved by the FDA for treatment of postmenopausal osteoporosis. Nonetheless, intermittent weekly or monthly therapy is believed to be biologically equivalent for fracture prevention and has become the standard of care.
More recently, both ibandronate and zoledronic acid have been approved for IV administration to treat postmenopausal osteoporosis. Whereas ibandronate is approved for quarterly administration, zoledronic acid is approved for once-yearly administration. During the 3-year Health Outcomes and Reduced Incidence with Zoledronic Acid Once Yearly (HORIZON) study period, annual IV administration of zoledronic acid led to significant decreases in vertebral (70% reduction), hip (41% reduction), and nonvertebral (25% reduction) fractures, with significant increases in BMD at the lumbar spine, hip, and femoral neck.14 In addition, administration of IV zoledronic acid within 90 days of surgical hip fracture repair and yearly thereafter was recently shown to reduce the incidence of any new clinical fracture by 35% and was associated with a 28% reduction in mortality.38 Further, in patients who have been treated with weekly alendronate for at least 1 year, switching to yearly zoledronic acid was not inferior to alendronate continuation, but yearly administration was preferred by patients.39 Whether IV preparations will become preferred bisphosphonate formulations for management of postmenopausal osteoporosis or after hip fracture is unknown. Nonetheless, it is clear that IV bisphosphonate delivery is particularly useful if adherence or gastrointestinal tolerance is a barrier to oral therapy or if patients prefer the relative convenience of IV bisphosphonate therapy.
Finally, several studies have focused on optimal timing of bisphosphonate therapy for management of osteoporosis in conjunction with other pharmacological agents with skeletal activity. Although combining a bisphosphonate with either estrogen or the selective estrogen-receptor modulator raloxifene leads to a slightly greater increase in BMD than treatment with a bisphosphonate alone, no good clinical trial data on fracture rates support routine use of these combinations.40,41 Other studies have evaluated patients receiving either recombinant full-length 1�84 human parathyroid hormone (PTH) or the PTH fragment 1�34 (teriparatide).42�44 In general, prior bisphosphonate treatment appears to blunt the PTH-induced anabolic skeletal response, as does concomitant treatment using bisphosphonate and either PTH or teriparatide.45,46 The most robust skeletal anabolic effects are seen in patients who receive initial PTH treatment and are subsequently maintained with bisphosphonate therapy.35,47,48
Glucocorticoid-Induced and Transplant-Associated Osteoporosis
Whereas bisphosphonates have become the primary therapeutic choice for treatment of postmenopausal osteoporosis, few recognize that glucocorticoid therapy leads to bone loss. A recent study found that most patients receiving long-term glucocorticoid therapy received neither regular BMD assessment nor a prescription for any medication for osteoporosis management.49 Numerous clinical trials have now determined that bisphosphonates are highly effective at limiting bone losses in patients receiving glucocorticoids or transplants. Recent work has shown that, in patients receiving a daily dose of at least 7.5 mg of prednisone, alendronate prevented bone loss more effectively than did the vitamin D3 analogue alfacalcidol.50 Further, in glucocorticoid-treated patients at high risk of fracture, including those with a history of fractures, those with rheumatoid arthritis, or those receiving high doses of glucocorticoid, bisphosphonate therapy is cost-effective.51
Accordingly, risedronate has been approved in the United States for both prevention and treatment of GIO and alendronate for the treatment of GIO. Both are more effective when calcium intake and vitamin D intake are adequate. As well, IV treatment with either pamidronate or ibandronate has been shown to limit skeletal loss from glucocorticoid therapy,52,53 although neither is yet approved for this indication. Notably, multiple studies have documented that both oral and IV bisphosphonate therapy are capable of limiting the bone loss that frequently occurs with either solid organ54�58 or bone marrow transplant.59�62
Finally, a recent study showed that patients with GIO treated with teriparatide had a greater increase in lumbar spine BMD and fewer new vertebral fractures than did patients who received daily alendronate during the course of 18 months.63 Whether teriparatide should supplant bisphosphonate therapy as the treatment of choice for patients with established osteoporosis who are receiving long-term glucocorticoid therapy remains unknown.
Immobility-Induced Osteoporosis and Other Causes of Acute Bone Loss
Immobilized patients, such as those with a recent spinal cord injury or cerebrovascular event, undergo rapid loss of bone, leading to a substantially increased risk of fracture, hypercalcemia, and frequently nephrolithiasis. Both oral (alendronate)64 and IV (pamidronate)65 bisphosphonate therapy have been shown to attenuate this bone loss and reduce biochemical markers of bone resorption. However, the number of clinical trials conducted using both these drugs remains small. Thus, fracture incidence, rates of nephrolithiasis, and long-term safety remain to be determined.
Unlike the generalized bone loss that occurs after immobilization, acute localized periprosthetic bone loss with associated implant loosening is a frequent complication in patients who undergo cementless total hip arthroplasty. Both alendronate66 and risedronate67 attenuate this acute periprosthetic bone loss of the proximal femur, although the long-term effect of bisphosphonate treatment on maintenance of implant integrity has not yet been reported.
Paget Disease of Bone
Whereas postmenopausal osteoporosis is characterized by generalized bone loss from increased osteoclast activity, Paget disease of bone involves 1 or more areas of disordered bone remodeling, in which accelerated osteoclast-mediated bone resorption is followed by imperfect osteoblast-mediated bone deposition.68 The resulting mix of poorly formed woven and lamellar bone frequently results in pain, fractures, and serious deformity, including bowing of weight-bearing long bones, skull enlargement, or numerous other skeletal deformities. As the cornerstone of therapy for Paget disease of bone, bisphosphonates profoundly suppress the increased bone resorption underlying the disease, generally leading to normalization of serum alkaline phosphatase levels used to monitor disease activity. Oral (alendronate69 and risedronate70) and IV (pamidronate71 and the recently approved zoledronic acid72) bisphosphonates are all FDA-approved for the treatment of Paget disease of bone and have largely replaced earlier FDA-approved therapies (non�nitrogen-containing bisphosphonates and calcitonin) because their ability to suppress osteoclast activity is superior.
Bisphosphonates in Malignancy
Many cancers are osteotropic and either metastasize to the skeleton (including but not limited to primary malignancies of the breast, prostate, lung, or kidney) or grow primarily within the bone marrow (multiple myeloma), where this growth frequently leads to hypercalcemia, severe bone pain, skeletal destruction, and pathologic fractures. Indeed, the skeleton is the most common site of metastatic disease, and 90% or more of patients with advanced cancer develop skeletal lesions.73
Breast Cancer
For patients with breast cancer metastatic to bone, treatment with IV preparations of pamidronate,74�76 zoledronic acid,77,78 and ibandronate79 has been shown to substantially relieve skeletal pain and reduce skeletal complications. Of the oral nitrogen-containing bisphosphonates, only ibandronate (given in a daily dosage of 50 mg) has been effective in reducing bone pain and limiting skeletal complications of breast cancer.80,81
Whether bisphosphonate use has an adjunct role in the treatment of women with breast cancer but no evidence of skeletal metastases is currently unknown but is suggested by the provocative finding that women with clinically limited operable breast cancer who received clodronate for 2 years had statistically significant reductions in development of bone metastases while receiving bisphosphonate therapy, as well as reductions in overall mortality when they were followed up for 6 years.82 Although bisphosphonate therapy for women receiving hormonal treatment of breast cancer has received less attention, the important role of limiting bone turnover to maintain skeletal integrity (particularly among premenopausal women in whom pharmacological estrogen deficiency has been introduced) has been more recently appreciated.83 Optimal bisphosphonate management strategies corresponding to numerous available pharmacological ovarian ablation regimens remain to be determined, although zoledronic acid (4 mg IV given every 6 months)84 has recently been demonstrated to prevent bone loss in premenopausal women receiving endocrine-based therapy for hormone-sensitive breast cancer. Likewise, in postmenopausal women with early hormone-dependent breast cancer, weekly oral risedronate was recently shown to prevent bone loss in those receiving aromatase inhibitor therapy.85
Prostate Cancer
Breast cancer is characterized by osteolytic lesions, but skeletal metastases from prostate cancer have been described as osteoblastic. The role of increased bone resorption in metastatic prostate cancer has recently been recognized.86 Among the bisphosphonates, only zoledronic acid has been demonstrated to reduce skeletal bone�related events in men with hormone-refractory prostate cancer,87,88 with an absolute risk reduction of 11% at 2 years compared with placebo.
As with women who undergo chemical hormonal ablation, men with hormone-responsive prostate cancer who receive androgen-deprivation therapy can benefit from judicious bisphosphonate use. Whereas IV pamidronate therapy prevented bone loss at both the hip and the spine in men with nonmetastatic prostate cancer who received gonadotropin-releasing hormone agonist therapy,89 a single annual dose of IV zoledronic acid was recently demonstrated to lead to increases in both spine and hip BMD (rather than the declines seen in patients who received placebo). These results demonstrate that annual IV bisphosphonate treatment can be a useful adjunct to maintain skeletal integrity in androgen-deprived men90 and are similar to results obtained with a more frequent dosing schedule.91 Oral risedronate at a daily dosage of 2.5 mg has also recently been shown to prevent BMD loss at the hip and been associated with a 4.9% increase at the lumbar spine.92
Multiple Myeloma
In multiple myeloma, clonal proliferation of malignant plasma cells within the bone marrow cavity results in osteolysis and skeletal destruction, accounting for much of the morbidity associated with the disease. Multiple studies have shown that both pamidronate and zoledronic acid have an important palliative role in reducing the incidence of hypercalcemia and skeletal bone�related events associated with myeloma,93�95 putting IV bisphosphonates at the center of current therapies to prevent and treat myeloma-associated bone disease. At present, no data support bisphosphonate therapy for patients with smoldering myeloma, myeloma without associated bone disease, or monoclonal gammopathy of undetermined significance, nor is oral bisphosphonate therapy recommended for management of myeloma-associated skeletal disease.
Given that patients with multiple myeloma have the highest incidence of ONJ among all oncology patients receiving bisphosphonate therapy, the choice of bisphosphonate, dosage, and duration of therapy have been the focus of considerable debate, cumulating in clinical practice guidelines from the American Society of Clinical Oncology96 and, more recently, a consensus statement from the Mayo Clinic Myeloma Group97 on the basis of a comprehensive review of the evolving literature. In the Mayo consensus statement, monthly infusion of pamidronate (because of a perceived higher risk of ONJ in patients receiving zoledronic acid) was favored, with discontinuation after 2 years if patients achieve remission and require no further myeloma treatment. If active treatment is still required, pamidronate can be continued at a reduced schedule of every 3 months. Although the International Myeloma Working Group generally agreed with the Mayo consensus statement, the group suggested that pamidronate therapy could be discontinued after a patient is in 1 year of clinical remission and that a reduced dosing schedule was not indicated.98 Thus, although bisphosphonates remain an important aspect of the pharmacological approach to myeloma bone disease, questions regarding their optimal use remain.
Other Malignancies
Use of bisphosphonates in other malignancies less frequently metastatic to bone, such as renal cell carcinoma, has been demonstrated to delay the onset and progression of skeletal disease,99 suggesting that patients with clinical conditions less commonly believed to affect the skeleton can also benefit from bisphosphonate therapy. At present, however, limited data support routine use of bisphosphonate therapy for other malignancies.
Bisphosphonate Therapy for Children
Although bisphosphonates have been used most extensively in adults, during the past decade they have become the mainstay of therapy for OI, a heritable skeletal disorder characterized by substantially diminished bone mass and severe fragility, usually resulting from mutations in the genes for type I collagen. A regimen developed by Glorieux100 of cyclic IV pamidronate (given in 3-day cycles every 2 to 4 months at an annual dose of 9 mg/kg) has been used most successfully, leading to an 88% increase in cortical thickness, a 46% increase in trabecular bone volume,101 and substantial improvement in functional status. More recently, several studies have demonstrated that oral alendronate can also lead to substantial increases in BMD and can limit fractures in OI affecting children.102�104 Although the precise mechanism by which bisphosphonates limit fractures in OI is unknown, histomorphometric analyses of bone biopsy specimens from patients with OI demonstrate increased rates of bone turnover resulting from increased osteoclast relative to osteoblast activity, leading to an overall loss of bone with each remodeling cycle.105 By specifically inhibiting osteoclast-mediated bone resorption, bisphosphonates presumptively allow bone-forming osteoblasts more time to promote bone formation, albeit in the setting of abnormal collagen matrix. Indeed, histomorphometric analyses of iliac crest biopsy specimens from patients with OI who had received pamidronate therapy demonstrated increased cortical thickness and number of trabeculae but no increase in trabecular thickness.101,106
Although bisphosphonate treatment is well established for OI in children, data are limited on efficacy and on risk of harm when bisphosphonates are used in children with osteoporosis secondary to chronic illness (such as cystic fibrosis, juvenile rheumatoid arthritis, or anorexia nervosa) or in those who have had serious burns. A recent systematic review of bisphosphonate therapy for children and adolescents with secondary osteoporosis concluded that too little evidence is available to support bisphosphonates as standard therapy, although treatment for periods of 3 years or less appears to be well tolerated.107 Well-constructed studies are required to develop clear guidelines to diagnose and treat all forms of osteoporosis in children.108
Finally, given the long skeletal half-life of bisphosphonates and evidence that pamidronate can be found in urine specimens up to 8 years after administration,109 care is warranted when considering bisphosphonate treatment for either adolescent or young girls who will reach reproductive maturity within a decade of treatment. At present, only limited, anecdotal data have assessed the safety of long-term pamidronate110 or other bisphosphonate treatment during fetal development.
Bisphosphonates in clinical practice are utilized to treat osteoporosis, Paget’s disease of the bone, bone metastasis, multiple myeloma, and other health issues with fragile bones. Although bisphosphonates are recommended as one of the first-line treatments for post-menopausal osteoporosis, research studies have previously discussed the adverse effects of this class of drug/medication. It’s essential for patients to talk to their healthcare professional regarding the treatment options for their injuries and/or conditions.
Dr. Alex Jimenez D.C., C.C.S.T. Insight
Clinical Concerns Associated with Bisphosphonate Therapy
Osteonecrosis of the Jaw
Among potential adverse clinical events associated with the use of bisphosphonates, none has received greater attention than ONJ. As reviewed by Woo et al,111 nearly all ONJ cases (94%) have been described in patients receiving high doses of IV bisphosphonates (primarily zoledronic acid and pamidronate) for oncologic conditions. Prevalence in patients with myeloma ranged from 7% to 10%, whereas up to 4% of patients with breast cancer developed ONJ.111,112 More recently, however, a reduced dosing schedule in patients with myeloma, in which IV bisphosphonate was given monthly for 1 year and then every 3 months thereafter, was shown to decrease the incidence of ONJ compared with monthly bisphosphonate infusions.113
Whereas the incidence of ONJ is estimated to be 1 to 10 per 100 oncology patients, the risk of ONJ appears to be substantially lower among patients receiving oral bisphosphonate therapy for osteoporosis, with an estimated incidence of approximately 1 in 10,000 to 1 in 100,000 patient treatment years, although this estimate is based on incomplete data.114 Associated risk factors appear to be poor oral hygiene, a history of dental procedures or denture use, and prolonged exposure to high IV bisphosphonate doses.115,116 Whether concomitant chemotherapy or glucocorticoid use leads to an increased risk of ONJ is unknown.117 Once established, care for ONJ is largely supportive, with antiseptic oral rinses, antibiotics, and limited surgical debridement as necessary leading to healing in most cases.118 Although evidence-based guidelines at this time have not been established for any single malignancy or bisphosphonate, careful attention to dental hygiene including an oral cavity examination for active or anticipated dental issues, both before bisphosphonate initiation and throughout treatment, is likely to be paramount.
Although use of bisphosphonates and development of ONJ have been temporally associated, a causal relationship has not been identified. Thus, despite the burgeoning scientific literature that has developed since the association between bisphosphonate therapy and ONJ was first reported in 2003,119 many fundamental questions remain unanswered. As a first step in this process, a task force convened by the American Society for Bone and Mineral Research recently provided a standardized definition of ONJ as the presence of exposed bone in the maxillofacial region that does not heal within 8 weeks after identification by a health care professional.114 Given the current paucity of information on the true incidence, risk factors, and clinical approach to both prevention and treatment, preclinical basic and animal studies, as well as well-designed clinical trials, are necessary to both identify patients at increased risk of development of ONJ and more fully understand the association between bisphosphonate therapy and ONJ.
Atrial Fibrillation
In addition to the concern for ONJ, another concern with bisphosphonate therapy, which has recently come to light, is atrial fibrillation. In the HORIZON Pivotal Fracture Trial, in which patients were treated annually with IV zoledronic acid, a statistically significant increase in the incidence of serious atrial fibrillation (defined as events resulting in hospitalization or disability or judged to be life-threatening) was noted.14 The etiology of this electrophysiologic abnormality is unknown. Whether other bisphosphonate preparations are associated with increased rates of atrial fibrillation is currently unknown, but recent post hoc analysis of data from the pivotal Fracture Intervention Trials120 and from a large population-based case-control study121 suggest a correlation between alendronate administration and a slightly increased incidence of atrial fibrillation, although a larger population-based case-control study showed no evidence of an increased risk of atrial fibrillation or flutter with alendronate use.122 To date, concerns for atrial fibrillation do not appear to extend to patients receiving risedronate,123 nor was an increased rate of atrial fibrillation seen in the HORIZON Recurrent Fracture Trial, in which patients received IV zoledronic acid after a hip fracture.38 Clearly, more studies examining the potential relationship between bisphosphonate use and atrial fibrillation are warranted, as are focused discussions between clinicians and patients either currently managed with or considering initiation of bisphosphonate treatment.
Oversuppression of Bone Turnover
Because bisphosphonates inhibit osteoclast activity, there has been some concern that prolonged bisphosphonate treatment leads to �frozen bone,� characterized by over-suppression of bone remodeling, an impaired ability to repair skeletal microfractures, and increased skeletal fragility. Although increased rates of microfractures have been found in dogs treated with high doses of bisphosphonates,124 this finding does not appear to be common among postmenopausal women with osteoporosis treated with either oral or IV bisphosphonate therapy,22,125 although isolated cases of severely suppressed bone turnover and associated fractures have been reported.126,127 Nonetheless, the optimal duration of bisphosphonate therapy for postmenopausal osteoporosis, and nearly all other conditions for which bisphosphonates are used, remains unclear.
Hypocalcemia
Hypocalcemia after bisphosphonate administration most frequently follows IV infusion and can occur in patients with high rates of osteoclast-mediated bone resorption (such as in patients with either Paget disease of bone128 or a substantial skeletal tumor burden129), previously unrecognized hypoparathyroidism,130 impaired renal function, or hypovitaminosis D before treatment.131 Treatment is largely supportive, with calcium and vitamin D supplements as appropriate.
Acute Inflammatory Response
Approximately 10% to 30% of patients receiving their first nitrogen-containing bisphosphonate infusion will experience an acute phase reaction, most commonly characterized by transient pyrexia with associated myalgias, arthralgias, headaches, and influenza-like symptoms. This rate declines by more than half with each subsequent infusion, such that a rate of 2.8% was found after the third infusion in the HORIZON trial.14 The acute phase response is believed to be the result of proinflammatory cytokine production by peripheral blood ?? T cells.132 Pretreatment with histamine receptor antagonists or antipyretics can reduce the incidence and severity of symptoms among susceptible patients. Occasionally corticosteroids are of benefit.
A relatively rare adverse effect of bisphosphonate therapy of which physicians should be aware is ocular inflammation (conjunctivitis, uveitis, episcleritis, and scleritis). This complication has been found to occur with both oral and IV bisphosphonate therapy. In the largest retrospective study to date, an incidence of approximately 0.1% was found in patients treated with oral risedronate.133 Fortunately, ocular symptoms usually resolve within a few weeks after bisphosphonate discontinuation.
Severe Musculoskeletal Pain
Although all oral and IV bisphosphonate preparations list musculoskeletal pain as a potential adverse effect in their prescribing information, the US FDA recently issued an alert highlighting the possibility of severe, incapacitating musculoskeletal pain that can occur at any point after initiation of bisphosphonate therapy.134 This severe musculoskeletal pain was distinct from the acute phase response described previously. Fewer than 120 cases had been reported by late 2002 for alendronate and mid-2003 for risedronate in total.135 At this time, both risk factors for and incidence of this adverse effect are unknown.
Other Potential Complications of Bisphosphonate Therapy
Other complications associated with the use of oral and IV bisphosphonate therapies are well recognized. Esophageal irritation and erosion can occur with oral bisphosphonate therapy, particularly in patients with known gastroesophageal reflux disease or esophageal stricture. Strict maintenance of an upright posture for 30 to 60 minutes after ingestion with a full glass of water, depending on the oral bisphosphonate, and the use of weekly rather than daily preparations are both likely to limit the risk of adverse effects. For patients unable to tolerate oral bisphosphonates, IV preparations (as noted previously) are now FDA approved and not associated with gastroesophageal irritation.
Bisphosphonate doses and infusion rates should be adjusted for patients with moderate to severe renal insufficiency. If used in patients with creatine clearance values lower than 30 mL/min, bisphosphonates must be used cautiously. Particularly in patients who receive IV preparations, bisphosphonates can lead to rapid deterioration of renal function,136,137 likely because of their local accumulation in the kidney. For patients with renal insufficiency who receive IV bisphosphonate therapy, renal function both before and after drug administration should be determined. In patients with mild to moderate renal impairment, oral bisphosphonates rarely lead to further deterioration in renal function, likely because of their poor absorption across the gastrointestinal tract and thus limited short-term bioavailability.
Unresolved Questions
Bisphosphonates have been and continue to be used for other conditions without an FDA-approved indication for therapy. As noted, these include various pediatric populations with low bone mass, incident fractures, and prolonged immobility. Many healthy premenopausal women with either radiographic osteopenia or osteoporosis without fractures and postmenopausal women with osteopenia but without fractures now receive bisphosphonate therapy. Until further studies address these important clinical questions, it is important to tell such patients that we currently lack sufficient data from well-controlled clinical trials to determine either benefits or risks assumed with these pharmacological interventions.
Role of Calcium and Vitamin D
Despite the good intentions of many practitioners to limit fractures in their patients by instituting bisphosphonate therapy, the importance of assuring adequate vitamin D and calcium intake both before and after starting bisphosphate therapy is frequently overlooked. Hypovitaminosis D is common among many patient populations that are also prescribed bisphosphonate therapy and is particularly common among elderly patients who frequently have limited sun exposure, reduced dietary intake, or some renal impairment. This vitamin D insufficiency or deficiency limits dietary absorption of calcium, leading to secondary hyperparathyroidism and loss of skeletal calcium to maintain normocalcemia. Accordingly, among elderly women with osteoporosis, the persistence of secondary hyperparathyroidism blunted the increase in BMD in the lumbar spine in response to weekly alendronate.138 Although currently available data offer no consensus on optimal serum levels of 25-hydroxyvitamin D, a level of 30 ng/mL (75 nmol/L) or more is generally considered to be adequate; vitamin D intoxication occurs only when levels are higher than 150 ng/mL (374 nmol/L).139 For a more complete review of the role of vitamin D in maintenance of skeletal health and for recommendations for vitamin D replacement, please refer to the excellent recent review by Holick.139
Although guidelines for the maintenance of optimal vitamin D levels have changed substantially as we appreciate that vitamin D insufficiency and deficiency affect a far greater proportion of the population than previously recognized, recommendations for optimal calcium intake have been modified only slightly since being addressed by an expert panel convened by the National Institutes of Health in 1994.140 The panel concluded that optimal calcium intake is estimated to be 1000 mg/d for both premenopausal and postmenopausal women receiving estrogen replacement therapy and 1500 mg/d for postmenopausal women not receiving estrogen. Men younger than 65 years were estimated to require 1000 mg/d of calcium and men older than 65 years to require 1500 mg/d.140 More recent recommendations from the National Osteoporosis Foundation have suggested a calcium intake of 1000 mg/d for both men and women younger than 50 years, with an increase to 1200 mg/d from age 50 years onward.141 These recommendations are consistent with those of the Food and Nutrition Board of the Institute of Medicine.142 Further recommendations for calcium intake in children are detailed in both the National Institutes of Health�s and Institute of Medicine�s guidelines.140,142
Conclusion
Since their introduction to clinical practice, bisphosphonates have transformed the clinical care of an array of skeletal disorders characterized by excessive osteoclast-mediated bone resorption. Accordingly, the informed and judicious use of bisphosphonates confers a clear clinical benefit for carefully selected patients that outweighs the risks associated with bisphosphonate use. Maintenance of adequate calcium and vitamin D intake is crucial for all patients receiving bisphosphonate therapy.
Acknowledgments
We thank James M. Peterson for assistance with the figures.
Preparation of this article was supported by a Mayo Career Development Award to Dr Drake.
Dr Khosla has received research support from Procter & Gamble and has served on the advisory board for Novartis.
Glossary
ATP – adenosine triphosphate
BMD – bone mineral density
DXA – dual-energy x-ray absorptiometry
FDA – Food and Drug Administration
GIO – glucocorticoid-induced osteoporosis
HORIZON – Health Outcomes and Reduced Incidence with Zoledronic Acid Once Yearly
IV – intravenous
OI – osteogenesis imperfecta
ONJ – osteonecrosis of the jaw
PPi – inorganic pyrophosphate
PTH – parathyroid hormone
WHI – Women�s Health Initiative
Footnotes
Individual reprints of this article are not available.
According to the article above, although the utilization of bisphosphonates in clinical practice provides healthcare professionals with new treatment options for skeletal disorders,�further research studies are still required. Information referenced from the National Center for Biotechnology Information (NCBI).�The scope of our information is limited to chiropractic as well as to spinal injuries and conditions. To discuss the subject matter, please feel free to ask Dr. Jimenez or contact us at�915-850-0900�.
Curated by Dr. Alex Jimenez
Additional Topics: Acute Back Pain
Back pain�is one of the most prevalent causes of disability and missed days at work worldwide. Back pain is the second most common reason for doctor office visits, outnumbered only by upper-respiratory infections. Approximately 80 percent of the population will experience back pain at least once throughout their life. The spine is a complex structure made up of bones, joints, ligaments, and muscles, among other soft tissues. Because of this, injuries and/or aggravated conditions, such as�herniated discs, can eventually lead to symptoms of back pain. Sports injuries or automobile accident injuries are often the most frequent cause of back pain, however, sometimes the simplest of movements can have painful results. Fortunately, alternative treatment options, such as chiropractic care, can help ease back pain through the use of spinal adjustments and manual manipulations, ultimately improving pain relief.
When we think of chiropractic care, our minds automatically jump to treatment for�work injuries, or issues stemming from aging. While spinal manipulations and other chiropractic treatment are�highly valuable in those situations, they are not the beginning and end of what chiropractic care can accomplish.�Here are four key�ways chiropractic care safeguards the whole family.
Adults who embrace the benefits of a chiropractor should consider treatment for their entire family, as it can provide unique benefits to each member regarding total wellness and quality of life.
Contents
Injury Prevention For The Whole Family
The best way to treat an injury is to avoid an injury. It sounds simple, but many individuals don’t think of their health this way. Chiropractic for each family member means that their spines will be well-maintained, aligned, joints are looser, and necks are relaxed. For younger family members, this means sliding into third base won’t pull a muscle, studying for that exam won’t cause headaches, and taking out the trash won’t hurt their backs (even though they may still gripe about it).
For the older family members, chiropractic treatment for prevention helps avoid workplace injuries, minimizes strains and sprains from gardening or other “weekend warrior” activities, and even aids in sleeping and stress relief.
Chiropractic care also helps every family member.
Increases Flexibility
As mentioned above, chiropractic treatment helps keep joints loose, and the entire body functioning properly. Flexibility is critical in performing physical activity, �lessening growing pains,�aging gracefully, and avoiding disease and injury. Spinal manipulation coupled with at-home exercises make it easy for each family member to be as limber as possible.
Enhances Healing
A wide variety of health issues, from headaches and backaches to immune diseases and digestive problems,�can be addressed through chiropractic care. That’s because, instead of treating the symptoms of an issue, chiropractors aim toward the cause of the problem. No matter what a person’s age, if they are dealing with issues caused by spinal misalignment or stiff muscles and joints, consulting with a chiropractor for treatment can speed up the healing process, decrease downtime, and lessen the chance of the issue recurring.
Reduces Performance Issues
Most individuals crave to perform at the highest level possible. Some examples are scoring�well on a test,�playing the best basketball game, driving safely, excelling at job duties, hiking a trail, and�giving a speech. We all want to do our best and be successful.
The holistic approach of chiropractic care helps us function at top performance. While pain takes the focus away from performing�well, and drugs can cause fuzziness and loss of concentration, chiropractic treatments give relief without side effects.�No matter a person’s age, chiropractic care helps his or her body be higher-functioning and ready for life’s challenges, regardless of the form they take.
Chiropractic care benefits patients of a wide array of ages�in a variety of ways. Family members should carefully consider the positive, long-lasting aspects of chiropractic treatment for themselves, their spouses, and children. A commitment to such treatment can decrease injury and performance issues, and increase flexibility, confidence, and success.
Cancer which develops in specific organs of the human body, including the lungs, breast, or prostate, among others, can sometimes spread into the bone, causing what is known as�metastatic bone disease, or MBD. Approximately more than 1.2 million new cancer cases are diagnosed every year, where about 50 percent can spread,�or metastasize, to the bones.
Through medical advancements, patients diagnosed with several different types of cancers, especially lung, breast, and prostate cancer, can live longer. However, primary cancers in more patients go through bone metastases, where they disperse�to the bone. Meanwhile, other types of cancers do not disperse so easily to the�bone. The most common cancers which develop in the organs and spread to the bones include:
Breast
Lung
Thyroid
Kidney
Prostate
Metastatic bone disease,�or MBD, can damage�and weaken the affected bone, causing pain along the site of spread.�Moreover, patients with MBD are at higher risk of suffering fractures or broken bones. The painful symptoms associated with MBD can make it challenging for the patient to engage in regular physical activities. The main concern of patients with metastatic bone disease is the loss in quality of life.
The extent of the effects of metastatic bone disease on a patient can change and is associated with how cancer has spread, which bones are affected, and how severe the bone harm is. Furthermore, there is a range of treatment choices available to treat MBD. Treatment help patients deal with pain to maintain activity levels and preserve their independence.
Contents
Metastatic Bone Disease Explained
The bones are the most common site of spread for cancers which begin in the organs, subsequent to the lung and the liver. Because many patients experience no painful symptoms of metastases to the liver and the lungs, these are often not discovered until the disease is in an advanced stage. In contrast, bone metastases are generally painful when they develop. Cancer most commonly spreads to these sites in the human skeleton:
Skull
Spine
Ribs
Upper arm
Pelvis
Long bones of the leg
Bone Damage
A tumor can completely destroy the bone at the site of spread, a process referred to as osteolytic bone destruction. Damage or weakened bones are most common in cancers which have spread from the lung, thyroid, kidney, and colon. New bone,�called osteoblastic, may also form due to the spread of cancer, more often seen in cancers from the stomach, bladder, and prostate.
Breast cancer often behaves in a combined osteolytic and osteoblastic method. Since the cancer cells secrete factors that interact with all the cells in the human skeleton, causing bone destruction, new bone formation, or both, osteolytic and osteoblastic metastatic bone disease happens. Also, breast cancer may commonly cause MBD in the hip and/or pelvis.
As a result of bone damage and weakness, patients with�metastatic bone disease are prone to fractures. Broken bones caused by MBD are termed “pathological fractures”.�Sometimes, the bone may be so weak that a fracture is imminent, termed “impending pathologic fractures”. Bedrest for lengthy intervals due to broken bones may result in chemical imbalances in the bloodstream, such as raised calcium levels, known as hypercalcemia. Patients with cancer that has spread to the spine can develop nerve damage which can result in paralysis or loss of using their arms and/or legs.
MBD Symptoms
A cancer patient who experiences any pain, especially in the back, arms, and legs should notify their doctor immediately. Pain which manifests without engaging in physical activities is especially concerning. The most common symptoms of�metastatic bone disease include:
Pain: MBD’s most prevalent symptom is pain. Patients may experience pain along their hip and/or pelvis, upper and lower extremities, and spine because the tumor may have damaged or weakened the bone.
Fractures: Broken bones, or fractures, can range from mild to severe and are generally a clear indication of the presence of MBD.
Anemia: The most common sites of spread, skull, spine, ribs, upper and lower extremities, and hip and/or pelvis, correspond to regions of bone marrow which produce high levels of red blood cells, responsible for carrying oxygen to cells. Anemia, or decreased red blood cell production, is a frequent blood abnormality with MBD.
MBD Diagnosis
Before following through with treatment for metastatic bone disease, it’s essential for the healthcare professional to understand the patient’s symptoms as well as their overall health and wellness. The doctor will ask for the patient’s medical history. After the medical history, the healthcare professional will perform a physical examination on the patient. The doctor may also utilize imaging diagnostics to help with the patient’s diagnosis.
Imaging Diagnostics
X-rays:�After the initial diagnosis, they may order x-rays. Because pain may often originate from other regions of the body, the healthcare professional will also order x-rays beyond the regions where the patient is experiencing discomfort. X-rays may tell an oncologist a great deal of information regarding how much bone is affected.
Other imaging tests: The doctor may also order a bone scan. This test can determine if other bones are involved with metastatic bone disease. In select situations, a computerized tomography, or�CT, scan and magnetic resonance imaging, or MRI, may be ordered, especially in scenarios where the spine or hip and/or pelvis are involved.
A variety of cancers can commonly cause metastatic bone disease, or MBD, throughout different regions of the human skeleton. Bone metastases can cause painful symptoms, ultimately affecting an individual’s quality of life. Research studies have demonstrated that metastatic bone disease in the hip and/or pelvis is a prevalent health issue associated with breast cancer. Treatment may vary on the progression of the problem.
Dr. Alex Jimenez D.C., C.C.S.T. Insight
Metastatic Bone Disease Treatment
Advances in surgical techniques, as well as radiation and medical treatment approaches, have significantly improved the quality of life of patients suffering from cancer that has spread to the bone from the site of origin. Treatment options for MBD are based upon how far the cancer has spread, which bones are affected, and how the bone was damaged or weakened.
In many cases of metastatic bone disease, cancer has progressed to multiple bony sites. As a result, treatment is concentrated on managing the symptoms of pain and bone weakness as it is not intended to be curative. The most common treatment option for MBD includes drugs and/or medications, and radiation to control pain and prevent additional spread of metastatic bone disease, and surgery to stabilize weak and broken bones.
Patients with metastatic bone disease require a team approach. A medical oncologist works closely with a radiation oncologist, and an orthopaedic surgeon. Diagnosis is essential in order to follow through with the best treatment approach. The scope of our information is limited to chiropractic as well as to spinal injuries and conditions. To discuss the subject matter, please feel free to ask Dr. Jimenez or contact us at�915-850-0900�.
Curated by Dr. Alex Jimenez
Additional Topics: Acute Back Pain
Back pain�is one of the most prevalent causes of disability and missed days at work worldwide. Back pain is the second most common reason for doctor office visits, outnumbered only by upper-respiratory infections. Approximately 80 percent of the population will experience back pain at least once throughout their life. The spine is a complex structure made up of bones, joints, ligaments, and muscles, among other soft tissues. Because of this, injuries and/or aggravated conditions, such as�herniated discs, can eventually lead to symptoms of back pain. Sports injuries or automobile accident injuries are often the most frequent cause of back pain, however, sometimes the simplest of movements can have painful results. Fortunately, alternative treatment options, such as chiropractic care, can help ease back pain through the use of spinal adjustments and manual manipulations, ultimately improving pain relief.
Femoroacetabular impingement, or FAI, is a medical state where additional bone develops in a single or multiple of the bones which make up the hip joint, giving the bones an irregular form. As a result, the bones may rub against each other since they do not fit together properly. This friction can ultimately harm the joint, causing pain, discomfort and limiting movement.
Contents
Anatomy
The hip is commonly characterized as a ball-and-socket joint. The acetabulum, which is part of the large pelvis bone, forms the socket of the joint. The ball of the joint is the femoral head, that is the upper end of the thighbone or femur. A type of soft tissue, known as articular cartilage, covers the surface of the ball-and-socket hip joint.
Articular cartilage makes a smooth, low friction surface which aids the bones to slide easily across each other through movement. The acetabulum is also lined by strong fibrocartilage, known as the labrum. The labrum shapes a gasket across the socket, forming a tight seal to provide stability as well as to help properly support the hip joint.
With femoroacetabular�impingement, bone spurs or bone overgrowth, surround the femoral head, across the acetabulum. The extra bone causes the hip joints to come into close contact and prevents them from gliding smoothly and without friction during movements. With age, this can cause labrum tears and osteoarthritis, or the breakdown of articular cartilage.
Types of Femoroacetabular Impingement
According to doctors, there are three types of femoroacetabular impingement, or FAI: pincer, cam,�and combined impingement.
Pincer:�This variety of impingement develops when bone extends outwards from the standard rim of the acetabulum. As a result, the labrum is crushed beneath the rim of the acetabulum.
Cam: In cam,�impingement of the femoral head causes the joint to be unable to rotate smoothly. A bump forms on the border of the femoral head which grinds the cartilage inside the acetabulum.
Combined: Combined impingement suggests that both pincer and cam types of femoroacetabular�impingement are found.
Causes of FAI
Abnormal development of the hip bones and joints throughout childhood is the most common cause of femoroacetabular impingement. However, it is the deformity of a pincer bone spur�or a cam bone spur which leads to joint damage and hip pain. If the hip bones and joints do not form normally, there’s little which can be done to prevent femoroacetabular�impingement.
Many people may have FAI and never�experience symptoms from the condition. When symptoms develop, however, it generally indicates that there is damage to the cartilage or labrum and the health issue may progress. Moreover, athletes are more likely to experience symptoms of femoroacetabular impingement, although exercise does not cause FAI.
Symptoms of FAI
The most common symptoms of femoroacetabular impingement include: pain and discomfort; stiffness; and limping.�Pain associated with FAI frequently occurs in the region of the groin, although it may also occur toward the exterior of the hip. Twisting, turning, and squatting may cause a sharp, stabbing pain while the pain is generally described as a dull ache.
Diagnosis of FAI
For the first consultation, the healthcare professional will discuss the patient’s hip symptoms and talk about their general health and wellness. They will also examine the patient’s hip. As part of the physical evaluation, the doctor will conduct an FAI impingement test by bringing up the patient’s knee then rotating it towards their opposite shoulder. If this recreates hip pain, the test is positive for femoroacetabular impingement.
Imaging Diagnostics
The healthcare professional may also order imaging diagnostics to help determine whether the patient has femoroacetabular impingement, or FAI. The following imaging diagnostics below can be used.
X-rays: These will show whether the hip has shaped bones of FAI, and provide images of the bone. X-rays may also reveal signs of arthritis.
Computed tomography (CT) scans: More comprehensive than a plain x-ray, CT scans help the healthcare professional determine the specific contour of the patient’s hips.
Magnetic resonance imaging (MRI) scans: These tests create pictures of soft tissue. They will help the doctor find harm to the labrum and articular cartilage. Injecting dye into the joint may make the damage or injury show up more clearly.
Local anesthetic: The doctor can also inject a numbing medication into the hip joint as a test. It affirms that FAI is the problem if temporary pain relief is provided by the local anesthetic.
�
Femoroacetabular impingement, or FAI, commonly affects the hip joint of many young and middle-aged adults. FAI occurs when the ball-and-socket joint of the hip causes abnormal friction and restricts range of movement. Furthermore, damage or injury to the articular cartilage or the labrum can affect the femoral head or the acetabular socket. Treatment options for FAI can range from alternative treatment options to surgery.
Dr. Alex Jimenez D.C., C.C.S.T. Insight
Treatment for Femoroacetabular Impingement
Non-Surgical Treatment
Lifestyle modifications:�The healthcare professional may recommend changes in physical activities that cause symptoms, simply altering the patient’s regular everyday routine.
Drugs and/or medications: The use of drugs and/or medications, such as ibuprofen, can be offered to help decrease painful symptoms and inflammation. The relief may only be temporary.
Alternative treatment options:�Treatment approaches like chiropractic care and physical therapy can help provide pain relief to patients with femoroacetabular impingement. Moreover, specific stretches and exercises can strengthen the muscles which support the joint and can boost range of movement. This can help relieve some stress and pressure on articular cartilage or the labrum.
Surgical Treatment
If imaging diagnostics and physical evaluations reveal additional hip joint damage and/or injury as well as the presence of other conditions and non-surgical treatment does not relieve the patient’s pain, the healthcare professional may recommend surgical interventions or surgery.
Arthroscopy
Femoroacetabular impingement can be treated with arthroscopic surgery. Arthroscopic surgical interventions are performed with thin instruments using little incisions. The surgeon then utilizes a small camera to look�inside the hip. The doctor can fix or clean out any damage to the labrum and articular cartilage by shaving the bulge on the femoral head and also trimming the bony rim of the acetabulum.
As the results of operation enhance, physicians will recommend surgery that is earlier for FAI. Surgical techniques continue to progress and at the future, computers may be utilized to guide the physician in reshaping and correcting the hip. The scope of our information is limited to chiropractic as well as to spinal injuries and conditions. To discuss the subject matter, please feel free to ask Dr. Jimenez or contact us at�915-850-0900�.
Curated by Dr. Alex Jimenez
Additional Topics: Chiropractic for Athletes with Back Pain
Back pain�is one of the most prevalent causes of disability and missed days at work worldwide. Back pain is the second most common reason for doctor office visits, outnumbered only by upper-respiratory infections. Approximately 80 percent of the population will experience back pain at least once throughout their life. The spine is a complex structure made up of bones, joints, ligaments, and muscles, among other soft tissues. Because of this, injuries and/or aggravated conditions, such as�herniated discs, can eventually lead to symptoms of back pain. Sports injuries or automobile accident injuries are often the most frequent cause of back pain, however, sometimes the simplest of movements can have painful results. Fortunately, alternative treatment options, such as chiropractic care, can help ease back pain through the use of spinal adjustments and manual manipulations, ultimately improving pain relief.
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