Darrell Hulisz, RPh, PhamD
Associate Professor, CWRU School of Medicine
Pharmacy Intern, ONU College of Pharmacy
Osteoporosis is a common condition affecting almost 10 million people in the United States. As the bone ages, bone mass and strength decreases along with micro architectural deterioration. Untreated osteoporosis can increase the chances of getting a fracture. This disease affects both men and women, however, is seen much more commonly in women. Certain medications increase a patient's for risk for developing osteoporosis including glucocorticoids, anticoagulants, anticonvulsants, aromatase inhibitors, cancer chemotherapeutic drugs, and gonadotropin-releasing hormone agonists. The current gold standard for diagnosis of osteoporosis in patients with a current fracture is a dual-energy x-ray absorptiometry (DXA) scan. Most DXA scans measure the bone density in specific parts of the body such as the spine, hip, and forearm. The DXA scores are based off of standard deviations of a young, healthy normal adult. The diagnosis for osteoporosis is 2.5 SD below the normal adult mean. This is scored as a T score.
The American College of Physicians (ACP) has released new guidelines for treating low bone mineral density or osteoporosis to prevent fractures for both men and women.1 The new guidelines exclude some medication utilized in the previous guidelines. For example, calcitonin has been excluded and is not widely used anymore. Etidronate and pamidronate have also been excluded because they are not approved to treat osteoporosis or reduce fractures. Denosumab was recently added to the guidelines. Denosumab is a human monoclonal antibody that was approved for the treatment of osteoporosis. Denosumab is a subcutaneous injection of 60 mg which is administered every 6 months. It works by binding to the RANKL inhibitor preventing osteoclasts from resorbing bone. It has moved to first line treatment for women to treat osteoporosis. Calcium and vitamin D may be added to osteoporosis treatment to prevent hypocalcemia. The benefits of adding these on is not clear, however, most studies of bisphosphonates added calcium and vitamin D onto their regimen. A recent meta-analysis concluded that calcium intake within tolerable upper intake levels (2000 to 2500 mg/d) is not associated with increased cardiovascular disease risk in healthy adults.2
For treating osteoporosis for women, the guidelines recommend treatment with alendronate, risedronate, zoledronic acid, or denosumab first line to reduce hip and vertebral fractures. These four options reduce radiographic vertebral, nonvertebral and hip fractures. Ibandronate, another bisphosphonate, only had sufficient evidence to show a decrease in vertebral fractures; it did not show strong evidence in reducing hip fractures therefore is not recommended first line. The main side effect for all three is mild-upper GI symptoms. Denosumab can leads to an increase in infection and rash; zoledronic acid has more side effects of atrial fibrillation, arthritis, arthralgia, headaches, and uveitis. Menopausal estrogen therapy, menopausal estrogen plus progesterone therapy, or raloxifene should not be used to treat osteoporosis in women (strong recommendation; moderate quality evidence). Estrogen therapy increases risk of cerebrovascular and venous thrombotic events. Raloxifene has been associated with hot flashes. The side effects for these medications outweigh the benefits, therefore, are not recommended.
In men with osteoporosis the ACP recommends using a bisphosphonate to reduce vertebral fractures.There are not many studies that evaluate the effectiveness of drugs used to treat osteoporosis in this population. One prospective study has demonstrated that zoledronic acid decreases the vertebral fractures in men with osteoporosis.3 In women, alendronate, risedronate, and zoledronic acid reduce vertebral, nonvertebral, and hip fractures and it was extrapolated to benefit the male population, and therefore are recommended.1
ACP recommends treating osteoporosis for five years although the evidence for this conclusion is weak recommendation; low quality evidence. Overall, the new guidelines are similar to previous guidelines. A new drug, denosumab, was added first line to treat women with osteoporosis and is subcutaneous injections every 6 months, however, is not recommended first line for men. Alendronate, risedronate, and zoledronic acid are other first line options to treat osteoporosis in women, and bisphosphonates are first line in men to prevent vertebral fractures.
- Qaseem A, Forciea MA, McLean RM, Denberg TD; Clinical Guidelines Committee of the American College of Physicians. Treatment of low bone density or osteoporosis to prevent fractures in men and women: A clinical practice guideline update from the American College of Physicians. Ann Intern Med. 2017 Jun 6;166(11):818-839.
- Chung M, Tang AM, Fu Z, Wang DD, Newberry SJ. Calcium intake and cardiovascular disease risk: An updated systematic review and meta-analysis. Ann Intern Med. 2016 Dec 20;165(12):856-866.
- Boonen S, Reginster JY, Kaufman JM, Lippuner K, Zanchetta J, Langdahl B, et al. Fracture risk and zoledronic acid therapy in men with osteoporosis. N Engl J Med. 2012 Nov 1;367(18):1714-23.