Osteoporosis is a skeletal disorder characterized by decreased bone mass and strength. In the United States, more than 1.3 million fractures are caused by osteoporosis each year. The most common first fracture is a wrist fracture, typically occurring between ages 50 and 70 in women. Hip fractures and fractures of the spine (compression fractures) also can occur and are most common in older patients. Osteoporosis can cause a great deal of suffering, including an increased risk of institutionalization or death.

Risk factors for the development of osteoporosis include:

Review of drug therapy for osteoporosis:

Calcium and vitamin D play an essential role in the formation and maintenance of bone integrity. Calcium and vitamin D dosing should take dietary consumption into account. Recommendations for daily intake from the NIH consensus statement on calcium are provided in the table.

* HRT = Hormone Replacement Therapy

Calcium carbonate is the salt containing the highest percentage of elemental calcium, and is readily absorbed from the GI tract. For this reason, it is often considered the formulation of choice for dietary supplementation. Patients with a history of peptic ulcer disease may not be able to tolerate calcium carbonate since it can cause a rebound increase in acid production. Patients with worsening symptoms of peptic ulcer disease or those with other side effects may benefit from a switch to another formulation. A summary of the calcium content of commercially available calcium supplements is provided

Elemental Calcium Content of Oral Calcium Supplements

Bisphosphonates (e.g., alendronate [Fosamax], risedronate [Actonel]) are considered the preferred treatment for osteoporosis. They bond to the surface of bone and inhibit osteoclast recruitment and activity. Placebo-controlled, randomized clinical trials have shown that both agents increase bone mineral density (BMD) at the spine and hip and reduce the risk of fractures by 30-50%. They also have been shown to reduce non-vertebral fractures in postmenopausal osteoporosis as well in as adults with glucocorticoid-induced osteoporosis.

Hormone Replacement Therapy (HRT) is indicated for the prevention of osteoporosis. Observational studies suggest that HRT replacement therapy increases BMD by 2-5% and decreases vertebral fractures by 50-80% and hip fractures by 25%. The Women's Health Initiative (WHI) trial found a 34% reduction in hip fractures and 23% reduction in other osteoporotic fractures with the use of HRT. The trial was halted prematurely because the incidence of breast cancer exceeded the stopping rules for the study. In evaluating whether a patient should remain on HRT, prescribers should discuss patient risk factors and family history to determine whether remaining on HRT makes sense for individual patients. (For more information on HRT, see Drug Therapy Volume XII, Issue 6 June 2002)

Raloxifene (Evista), a selective estrogen receptor modulator, acts by inhibition of osteoclast activity. Raloxifene also lowers serum lipids and inhibits breast cancer without stimulating the endometrium. Raloxifene increases vertebral BMD by 2.6% and hip BMD by 2.1%. Raloxifene therapy decreases vertebral fractures by 40% but has no effect on the non-vertebral fracture rate.

Calcitonin Salmon (Miacalcin) acts by the inhibition of production and activity of osteoclasts. Therapy with calcitonin increases vertebral BMD by 3% and decreases vertebral fractures by 31%. Calcitonin also provides analgesia to patients suffering pain associated with vertebral fractures. Therapy with calcitonin should be reserved for patients who are intolerant or unwilling to take bisphosphonates or selective estrogen receptor modulators.

References:

Chesnut III CH, Silverman S, Andriano K, et al. A randomized trial of nasal spray salmon calcitonin in postmenopausal women with established osteoporosis: the PROOF study. Am J Med. 2000; 109:267-276.

Cummings SR, Black DM, Thompson DE, et al. Effect of alendronate on risk of fracture in women with low bone density but without vertebral fractures: Results from the Fracture Intervention Trial. JAMA. 1998; 280 (24):2077-82.

Ettinger B, Black DM, Mitlak BH, et al. Reduction of vertebral fracture risk in postmenopausal women with osteoporosis treated with raloxifene: Results from a 3-year randomized clinical trial. JAMA. 1999; 282:637-645.

Harris ST, Watts NB, Genant HK, et al. Effects of risedronate treatment on vertebral and nonvertebral fractures in women with postmenopausal osteoporosis: A randomized controlled trial. JAMA. 1999; 282:1344-1352.

Hulley S, Grady D, Bush T et al. Randomized trial of estrogen plus progestin for secondary prevention of coronary heart disease in postmenopausal women. JAMA. 1998; 280(7): 605-613.

Drug Facts and Comparisons Staff. Minerals and electrolytes, oral in Facts and Comparisons. St. Louis: Facts and Comparisons.1999.

McClung MR, Geusens P, Miller PD, et al. Effect of risedronate on the risk of hip fracture in elderly women. N Engl J Med. 2001; 344:333-340.

NIH Consensus Development Panel on Osteoporosis Prevention, Diagnosis, and Therapy. Osteoporosis prevention, diagnosis, and therapy. JAMA. 2001; 285(6):785-795.

Ray NF, Chan JK, Thamer M, et al. Medical expenditures for the treatment of osteoporotic fractures in the United States in 1995: Report from the National Osteoporosis Foundation. J Bone Miner Res. 1997; 12(1):24-35.