Author: Simon Kipersztok, M.D., University of Florida

Treatment of Osteoporosis

The three commonly accepted therapies available for postmenopausal osteoporosis are hormone replacement therapy (HRT), bisphosphonates and calcitonin. The three treatments work as anti-resorptive agents. Other adjuncts to this therapies are often recommended and these include adequate calcium intake, vitamin D and weight bearing exercise. There are other agents available in clinical medicine that have been shown to improve BMD and these include drugs such as tamoxifen (commonly used as an adjunct in the treatment of breast cancer), thiazide diurectics (used in the treatment of hypertension) and sodium fluoride which is presently undergoing evaluation by the Food and Drug Administration (FDA) in order to be approved for the treatment of osteoporosis. Ideally, any drug used in the treatment of osteoporosis should improve BMD and decrease the risk of fracture at all the anatomical sites commonly affected by the disease and with a magnitude that either opposes or reverses the naturally occurring bone loss observed in all humans as age increases. It should also have minimal side effects and be inexpensive. There are no published guidelines with regards to which therapy for osteoporosis should be used first and on what patients. The decision must be individualized based on the patient's clinical profile and preferably made with the patient after a full discussion of the options available, their benefits and potential risks.

For women who have no contraindications to its use, HRT should be considered as the preferred initial therapy because it prevents decreases in BMD and decreases the risk of fracture while providing other health benefits. HRT eliminates the disturbing hot flushes as well as other hypoestrogenic symptoms commonly experienced by a sizable number of postmenopausal women (such as difficulty sleeping and vaginal dryness). Most importantly, HRT has a beneficial effect in the cardiovascular system and in current users it has been shown to favorably improve the lipid profile and decrease the incidence of heart attacks. Other possible benefits of HRT include the improvement of some cases of urinary incontinence and its potential to enhance the collagen content of the skin.

Compliance can be a problem with HRT for two main reasons. The first reason is that many women are concerned about the potential of estrogen to increase the incidence of breast cancer although many authorities feel that the large amount of data generated in the last 50-60 years on this issue is neither compelling nor consistent or coherent. The second reason is that for women who have a uterus, estrogen must be prescribed with a progestin in order to significantly minimize the risk of endometrial hyperplasia or neoplasia. The addition of the progestin to the treatment can cause side effects such as unscheduled vaginal bleeding and bloating.

The bisphosphonates are a class of compounds structurally related to pyrophosphate which plays an important role in bone metabolism. The most widely used bisphosphonates are etidronate (Didronel-trademark) and alendronate (Fosamax-trademark). Both compounds can prevent decreases of BMD and prevent fractures although the magnitude of BMD increase seen during therapy with alendronate is probably the largest compared to all the other available treatments for osteoporosis. Both compounds have poor bioavailability when ingested with food and therefore to facilitate absorption they must be taken on an empty stomach and with a large glass of water in the upright position. Also, patients should not eat for 30-60 minutes after ingesting their medication. Pill induced esophagitis can occur in a very small number of patients. Most of the patients recover after the drug is discontinued. Therefore, the drug should not be used in patients with active upper gastrointestinal problems [6]. Unlike alendronate which is dosed daily, etidronate must be taken every three months for 14 days. The reason for this intermittent cyclical regimen is that the etidronate, if taken daily, has the potential of causing demineralization of bone. Both drugs are also used in the treatment of Paget's disease of the bone and are excreted by the kidney.

Calcitonin is a hormone produced by the parafollicular cells of the thyroid gland. The hormone is involved in calcium metabolism and is produced by many members of the animal kingdom including fish. It is FDA approved for the treatment of osteoporosis and a recently marketed nasal formulation of salmon calcitonin is available for clinical use. The data on the beneficial effects of salmon calcitonin in the treatment of osteoporosis is limited to a relatively small number of patients in whom a benefit was found in improving osteoporosis mostly in the vertebral spine. Calcitonin may not be used in patients allergic to fish products and in some patients antibodies to the fish hormone can diminish its bioavalability and consequently its efficacy. One uniquely beneficial advantage that this drug has is its analgesic effect on back pain which can lead to a reduction in the amount of pain medication required by osteoporotic patients.

The use of combinations of the therapies mentioned above has not been extensively studied. One study on a small number of patients showed that BMD in the vertebrae and the hip improved significantly when intermittent cyclical etidronate was added to HRT [7]. Some authorities in the field of osteoporosis have expressed their concern that the use of more than one anti resorptive agent can impair the metabolic functions that osteoclasts and osteoblasts have in reparative processes in bones. Yet, no data is available that can validate such concern. In very discrete and unique situations it would make sense to use the combination therapy. One such instance is where an osteoporotic woman requires HRT for alleviation of post-menopausal symptoms and bone loss continues to occur despite treatment. The addition of a second antiresorptive agent, preferably a bisphosphonate, is then reasonable.