Posted @ 8/30/2012 10:42 AM by Dr David Feinstein | Files in VitD,Osteoporosis,FRAX Score
is a common skeletal disease in older populations, which leads to
about two million fractures annually in the US. It is a silent
disorder, characterized by decreased bone strength, predisposing to
an increased risk of fracture. Bone strength reflects two major
features, bone density and bone quality. Bone quality includes such
factors as the health of the collagen component of bone, and the
architecture of bone. Bone quality however, cannot practically be
quantified. For now, measurement of bone density remains the primary
technique for measuring bone strength and monitoring the treatment
Bone densitometry is the tool used to measure bone density. The device measures the bone density in the lower spine (T1-T4) and in the hip (the entire or total hip and the femoral neck portion of the hip). A measurement called the T Score compares an individual’s bone mineral density (BMD) with the mean value for a young normal person. The difference is expressed in how many standard deviations (a statistical term) an individual’s bone density measurement is from the young normal mean. A normal bone density is defined as a standard deviation from the mean of up to -1. Osteopenia is thought to be present when an individual’s BMD is between -1 and -2.5 standard deviations below the mean. Osteoporosis is present when the patient’s bone density is less than -2.5 standard deviations below the mean. The more negative the standard deviation is, the more severe the osteoporosis.
About 80% of patients with osteoporosis are women. Most of them are post- menopausal. Menopause is when acceleration of bone loss occurs. At age fifty, the lifetime risk of developing fractures is about 39% for white women, and 13% for white men. While white women are most often affected, women of all races are at risk. By age sixty, half of all women have osteopenia or osteoporosis.
More women have osteoporotic fractures than new strokes, heart attacks, and invasive breast cancer combined. Hip fractures are the most serious. The mortality during the first year after a hip fracture is greater than 30% for men, and 17% for women. Vertebral (spine) fractures cause 70,000 hospital admissions annually and commonly cause chronic pain and deformity. Fractures of the forearm generate 530,000 office visits annually in the US. Because the incidence of osteoporotic fractures increases with age, the number of such fractures is expected to dramatically increase as our population ages.
Bone is a living tissue. Parts of bone are continuously removed and replaced with new bone. This process of bone removal and bone replacement is called the bone remodeling. The entire skeleton, by this process, is replaced every three years. At any one time, there may be a million excavation sites going on somewhere in your skeleton. The body identifies a weak area of bone (microscopic stress fracture or injury), and recruits a particular cell called an osteoclast, to attach itself to bone and resorb a localized area of bone (acid released by the osteoclast digests the bone). After this phase is completed, another type of cell called an osteoblast is recruited to the excavation site, and this cell lays down collagen, which then calcifies, and fills in new bone what had been removed. In younger life, the entire process of bone remodeling is complete and the amount of bone laid down is equal to the bone removed. The bone density of the skeleton therefore remains stable. After menopause however, and the withdrawal of estrogen, the process of bone remodeling becomes accelerated and incomplete. The amount of bone deposited in a bone remodeling cycle is less than the amount of bone that was resorbed. Because this is taking place in a million sites all over the skeleton, the end result is that there is a progressive loss of bone, which results in a decrease of the BMD.
We now know that estrogen deficiency causes the release of an excessive amount of a substance called RANK Ligand from bone. RANK Ligand combines with its receptor (recognition site) on osteoclast precursors (cells that will evolve into osteoclasts) and on osteoclasts to cause them to become more numerous and more aggressive. The hungry osteoclasts excavate larger and deeper areas of bone. This can lead to the destruction of the architecture of bone, making it more difficult for the osteoblast to adhere itself to the area of excavation and to replace that which was removed.
Estrogen replacement at the time of menopause can reduce the rate of bone loss (by reducing the rate of RANK Ligand released from bone. Estrogen though, is no longer routinely prescribed to women at the time of menopause because of other effects of estrogen that can have a negative effect on health. These include such consequences as a slight increase in the incidence of blood clotting, breast cancer and possibly heart disease. The decision to give estrogen at the time of menopause requires a balanced decision weighing risk and benefit and is strongly affected by the patient’s degree of vasomotor symptoms such as hot flashes.
The primary identifiable cause for osteoporosis is (other than genes), estrogen deficiency. Other so called secondary causes for bone loss however, may be present and should be considered.
Vitamin D Deficiency
Vitamin D is required to adequately absorb calcium from the gut. Vitamin D can be made in the skin as a consequence of sun exposure; however current use of sunscreens has reduced the amount of Vitamin D that is naturally synthesized. The current recommendation for Vitamin D intake is between 1000 and 2000 units daily. Vitamin D levels can be measured and the ideal blood level is a value greater than 30. If patients are severely deficient in Vitamin D, then much larger doses of Vitamin D can be used such as 50,000 units weekly for three months.
Inadequate calcium intake in the diet
Calcium is found primarily in dairy products, green leafy vegetables and sardines. A diet devoid of dairy products usually contains about 300 mg. of calcium. The current recommendation for calcium intake is about 1200 mg. per day between diet and supplements. Each dairy product contains about 300 mg. of calcium. If a patient consumes two different dairy products per day, he or she would probably need a supplement of about 500 mg. of calcium per day. Too much of a good thing can cause problems. Diets that are extremely high in calcium could predispose to kidney stones and possibly calcification of blood vessels. Calcium carbonate is less expensive however acid-blocking drugs used to treat reflux and gastritis can interfere with its absorption. Calcium citrate (Citracal) can be adequately absorbed even when used concomitantly with acid blocking medications. Probably no more than 500 mg. of calcium should be taken at any one time.
If there were not enough reasons before, not to smoke, this is one more.
The definition of excess alcohol is 3 or more units of alcohol per day, beer, spirits or wine.
Prolonged periods of inactivity
This can occur following a stroke, or orthopedic surgery. Astronauts who spend long periods of time in space are faced with accelerated loss of bone as a consequence of being weightless.
Use of certain drugs
Prolonged use of steroids, overtreatment with thyroid hormone, and anticonvulsant medications are all associated with accelerated bone loss.
Rheumatoid arthritis, hyperparathyroidism, and cancer particularly myeloma.
Poor nutrition especially during adolescence
This can result in inadequate bone being laid down during adolescence, which results in a decrease in the peak bone mass which is the maximum bone that a person will ever have. Therefore when bone loss occurs with aging, the point at which it begins is at a lower point than average.
Eating Disorders or excess thinness
lead to menstrual irregularity or amenorrhea (no period). The
mechanism is low body fat composition that alters pituitary function
leading to estrogen deficiency.
When a patient is being evaluated for osteoporosis these secondary causes of bone loss should be considered and corrected if possible.
In addition to prescribing an adequate amount of calcium and Vitamin D, and weight bearing exercises such as walking, jogging and rowing, your doctor may choose to treat with a medication. Oral bisphosphonates are currently the most common therapy for osteoporosis. The three most utilized are Fosamax (alendronate), Actinol (risedronate), and Boniva (ibandronate). They have all been shown to reduce vertebral fractures. It is unknown however, whether they are equally effective in reducing nonvertebral fractures. This class of drugs also includes Reclast (zolendronic acid), which is a once a year drug given over a thirty minute IV Infusion. All these medications work because they share two properties, (1) bind to bone and (2) inhibit a key osteoclast enzyme (framesyl pyrophosphate synthase). After absorption the drug is deposited on the surface of bone where it is then ingested by osteoclasts. Osteoclast activity is then reduced leading to decreased bone resorption. This class of drugs is poorly absorbed in the GI Tract, with less than 1% of the dose actually absorbed. The drugs are usually given on an empty stomach, washed down and out of the esophagus with a full glass of water, and patients are advised not to have any other food or drink for 30-60 minutes. This is because food or drink other than water will reduce further the absorption of what is already a poorly absorbed medication. Following ingestion, the patient should remain upright for at least the next hour, to reduce the chance of the medication getting back into the esophagus where it can cause irritation. Actinol (risedronate) has recently become available in an enteric-coated preparation called Atelvia that eliminates the waiting time to eat or drink. This could lead to improved compliance and absorption. Studies have shown that patients for one reason or another, are not particularly good at taking oral bisphosphonates and apparently these drugs don’t work if they are not taken as prescribed.
Prolia (denosumab) is a new medication that is a subcutaneous injection that is given every six months. The drug is classified as a monoclonal antibody. It is directed at RANK Ligand that is overexpressed following menopause. The binding of Prolia to RANK Ligand reduces the availability of RANK Ligand to bind with RANK on preosteoclasts and osteoclasts. This results in fewer osteoclasts formation and lesser aggressive osteoclasts. This in turn leads to decreased bone resorption. Prolia is somewhat more powerful in inhibiting bone resorption than the oral bisphosphonates. Subcutaneous injections of Prolia avoid the GI Tract and therefore can be better tolerated by some people who have GI complaints while on an oral bisphosphonate. Prolia has been associated with an increased incidence of reoccurrence of chronic skin conditions such as eczema and there has been a slightly higher incidence of skin infections reported.
All the drugs so far mentioned interfere with osteoclast function (bone resorption), but there is one FDA approved drug that can activate bone formation by stimulating osteoblast activity. This drug is Forteo (teriparatide), which is considered to be an anabolic drug and not an anti-resorptive drug. Forteo is a form of parathyroid hormone (PTH). Persistent exposure to PTH as occurs in patients who have hyperparathyroidism, usually have accelerated rates of bone loss, but when the same hormone is given intermittently such as daily subcutaneous injections, the result is a paradoxical response with stimulation of osteoblasts to lay down more bone. This drug has been approved for use for a maximum of two years. This is because in rats, Forteo has been shown to cause a form of bone cancer called osteosarcoma. This complication has not been shown to occur in humans. Treatment has been limited to patients with more extreme forms of osteoporosis. This includes patients who have had multiple previous fractures or who have failed to respond to oral bisphosphonates. After completing a course of therapy with Forteo, it needs to be followed by a bisphosphonate or Prolia in order to maintain the improvement that was achieved while taking Forteo.
All of the antiresorptive drugs, including bisphosphates and Prolia, have been associated with a small risk of a condition called osteonecrosis of the jaw (ONJ). This can occur spontaneously but it is far more likely to occur associated with a tooth extraction. The end result is a local infection and delayed healing of the bone. The chance of developing this problem is much increased if the patient has also been on drugs that affect the immune system such as steroids or chemotherapy. Stopping oral bisphosphonates before the procedure is not likely to be helpful because of the very long half-life of bisphosphonates in bone. Before starting any form of antiresorptive treatment, patients should complete any dental work that is necessary.
An even rarer problem with antiresorptive drugs is atypical fractures, which mean fractures that occur in bones or parts of bones where osteoporotic fractures rarely occur. This has been attributed to extreme over-suppression of bone turnover. Fear of this complication is exaggerated, and the benefits of these drugs are far outweighed by the 50% reduction that occurs in osteoporotic fractures in such locations as spine, hip, wrist, pelvis, clavicle and humerus. Different dosing regimens, including drug holidays from bisphosphonates, are being evaluated to reduce further this rare complication, but there are no studies available yet to make a firm recommendation. Some individuals may have been given bisphosphonates inappropriately (when they were not indicated) and it is with these patients that I am most likely to recommend a drug holiday by stopping the medication.
Drug therapy is indicated in patients who:
1) have already had an osteoporotic fracture (each fracture increases the likelihood of subsequent fractures).
2) have a T Score in the spine or the hip of less than -2.5 standard deviations from the mean of a young normal population.
3) have a T Score of -1.5 to -2.5 (osteopenia) and who have other factors that would increase their chance of having a fracture such as a strong family history of osteoporosis, tendency to fall, certain drugs, rheumatoid arthritis.
The decision to treat osteoporosis can be clear-cut or it can be questionable. In order to help make that decision, a scoring system has been devised called the FRAX Score, the score. This scoring system utilizes the bone mineral density (BMD) in the femoral neck of the hip and other identifiable risk factors that predispose to fractures. The FRAX Score estimates what a patients’ probability is of having a fracture in the hip or any major osteoporotic fracture over the next ten years. If the probability of a hip fracture is estimated to be greater than or equal to 3%, or the probability of any major osteoporotic fracture is greater than or equal to 20%, then the evidence would favor intervention with a medication such as a bisphosphonate. The FRAX calculator can be found on the internet at www.shef.ac.uk/frax/
Because osteoporosis can be a silent disease, compliance is a huge problem and patients, unfortunately, are inconsistent in taking their medications. Generic preparations of Actonel and Fosamax are available although these drugs should be equivalent to the branded preparations. This may not in fact, be the case. The reason for the difference could be related to a high incidence of GI problems with these generic drugs and therefore compliance. It is also possible that the generic drugs have reduced bioavailability compared to the branded drugs and at least one study showed a 40-50% lower BMD increase when generic compounds were used.
Other treatments such as plant phytoestrogens have not been adequately evaluated to support their use. Fluoride, which has been helpful in preventing tooth decay, may also be helpful to improve bone density but the effect can vary with the dose and can, in fact, have a paradoxical effect on bone to increase fracture rate. Currently no FDA approved preparation of fluoride is available. Strontium, which is available in Europe and seems to have an anabolic effect on bone, is not available in the US. Calcitonin (myacalcin) has a relatively weak effect on bone and should be considered only if all other drugs cannot be tolerated. Evista, which has both antiestrogen and estrogen like properties, has been shown to maintain bone density. Evista has also been shown to reduce the incidence of estrogen dependent breast cancer. Evista has been used to treat osteopenia and milder forms of osteoporosis.
Bone density testing should be done in all women 65 years and older. Bone density testing could be done between menopause and age 65 if patients have risk factors that put them at higher risk of developing osteoporosis. These include a strong family history of osteoporosis, rheumatoid arthritis, prolonged use of steroids. Bone density testing can be done every two to five years if a normal bone density has been documented. Bone density can be done yearly if a patient has been started on a medical treatment in order to assess response to treatment.
For a drug to be effective, bone density does not necessarily need to increase. If patients maintain their bone density, the fracture reduction is quite similar to patients whose bone density increases. The purpose of repeat bone density measurements is therefore not necessarily to document the increase of bone density but rather to identify patients whose bone density decline during treatment. A decline in bone density might imply noncompliance with the treatment or unrecognized secondary causes of bone loss such as Vitamin D deficiency or hyperparathyroidism. If no secondary cause can be found, then a switch to a more potent treatment or a referral to a physician who specializes in osteoporosis management is advised.
Fractures tend to occur when people fall down. Therefore steps to avoid falls are essential. People are most likely to fall at night on the way to the bathroom. Modifications in the bathroom such as the addition of handrails could prevent falls. Patients who are highly likely to fall could wear hip protectors, which are pads that go over the hips and can be purchased over the internet.
Osteoporosis is a common medical problem that can lead to fractures which can be life changing and life threatening. Osteoporosis can be accurately diagnosed and under current treatments can reduce the incidence of fracture by about 50% or more. The goal is to try to prevent osteoporosis through better nutrition during adolescence and then through adult life. We want to make sure that patients who are at risk of fractures get the medications that they can afford, tolerate and continue to take.
David Feinstein, MD FRCP(C), FACP, FACP