Overview of the Management of Osteoporosis in Women
Lindsay Baun, PharmD PGY-1 Pharmacy Practice Resident Lebanon VA Medical Center Lebanon, Pennsylvania
Tricia M. Russell, PharmD, BCPS, CDE Assistant Professor, Department of Pharmacy Practice Wilkes University Nesbitt College of Pharmacy and Nursing Wilkes-Barre, Pennsylvania
9/20/2011
Osteoporosis, a term meaning “porous bones,” is a silent disease that occurs as a result of reduced bone formation and increased bone resorption.1 These factors compromise bone structure, leading to microfractures, which can later develop into clinical fractures.2 Complications of fractures include disability, body deformity, depression, pain, and death.2 Prevention of osteoporosis entails identifying secondary causes in order to modify risk factors, if applicable. Treating osteoporosis involves the use of prescription medications, calcium and vitamin D supplementation, and nonpharmacologic therapies, such as appropriate diet, exercise, and smoking cessation. The impact of a pharmacist’s knowledge of osteoporosis management can help ensure the proper use of medications, appropriate vitamin supplementation, and patient counseling on recommended lifestyle changes.
Prevalence
Osteoporosis is present in 44 million Americans, and the majority of this population is over 50 years of age.3 Women aged 50 years and older have a 50% chance of breaking a bone due to osteoporosis.4 To compare the incidence of other disease states with the prevalence of osteoporosis in women, the risk of hip fracture is more than the collective risk of uterine, ovarian, and breast cancer.4 Complications of hip fractures include an increased risk of future fractures and mortality. Within the first year of a hip fracture, the risk of mortality increases 10% to 20%, and future fracture risk multiplies by 2.5-fold.
Risk Factors
The leading causes of osteoporosis are separated into nonmodifiable and modifiable risk factors . Women are more at risk for osteoporosis after menopause due to a reduction in estrogen, which plays an important role in bone protection.4 In addition, peak bone mass occurs between the ages of 18 and 25 years and slowly declines from this age onward.2 One study completed in 2007 specifically evaluated risk factors for osteoporosis in postmenopausal women.5 The results of this study demonstrated an increased risk of osteoporosis in women with a history of fracture, total body weight less than 127 lb, and the use of anticoagulants, such as warfarin or heparin.
Diagnosis
The diagnosis of osteoporosis is determined by measuring one’s bone mineral density (BMD), which serves as a predictor of future fracture risk. The National Osteoporosis Foundation (NOF) provides guidelines on the most up-to-date recommendations regarding diagnostic criteria
Pharmacologic Treatment
Calcitonin: There are two calcitonin agents (Fortical, Miacalcin) currently FDA approved for the treatment of osteoporosis in women who are postmenopausal for at least 5 years. Calcitonin is involved with calcium regulation and directly inhibits osteoclastic bone resorption.7 Both medications are generally safe and offer different routes of administration—intranasal and SC. A study published in 2000 compared the efficacy of alendronate versus calcitonin for osteoporosis in postmenopausal women. Increases in BMD and reductions in bone turnover were significantly greater at 12 months with alendronate compared to intranasal calcitonin. The results of this study further verify the use of bisphosphonates as first-line agents, but offer calcitonin as a therapeutic alternative for osteoporosis.14
Selective Estrogen Receptor Modulator (SERM): Raloxifene is the only SERM approved by the FDA for the prevention and treatment of osteoporosis in postmenopausal women. It is also indicated for breast cancer prevention. Raloxifene has similar effects as estrogen in preventing bone loss, but potentially antagonizes estrogen in uterine and breast tissue. In addition, raloxifene increases BMD and reduces bone resorption. Over 3 years, raloxifene has shown vertebral fracture reductions of 30% in patients with a prior fracture and 55% in patients without a previous fracture.2 Raloxifene has shown an increased risk of venous thromboembolism (VTE); therefore, its use is contraindicated in patients with a history of VTE.7
Parathyroid Hormone Analogue: Teriparatide is FDA approved for use in patients at high risk of fracture in postmenopausal women, men, and patients on prolonged glucocorticoid therapy.2 The mechanism of action is similar to that of the endogenous form of parathyroid hormone, which functions to promote osteoblast activity. In addition, the drug increases the absorption of calcium in the gastrointestinal tract and reabsorption through the renal tubules. Efficacy data at 18 months demonstrated a 65% reduction in vertebral fractures and a 53% reduction in nonvertebral fractures.2 Generally, this medication is well tolerated, but should be avoided in patients who are at an increased risk of osteosarcoma.7 Teriparatide is not recommended for use longer than 2 years, due to limited safety data. Limitations of therapy include daily SC injections into the abdomen or thigh and higher cost compared to other osteoporosis medications.7
Monoclonal Antibody: Denosumab is a new, fully human monoclonal antibody. This agent acts by binding to receptor activator of nuclear factor kappa-B ligand (RANKL), which is an important cytokine essential for the formation, activation, and survival of osteoclasts.15 Denosumab prevents the binding of RANKL to its receptor, RANK, on osteoclasts, which results in reversible inhibition of bone resorption by osteoclasts and increases BMD.15 In 2009, the Fracture Reduction Evaluation of Denosumab in Osteoporosis Every 6 Months (FREEDOM) trial was published.16 The objective of the study was to assess denosumab versus placebo over 3 years in the primary end point of reducing new vertebral fractures. Results demonstrated a 69% reduction in vertebral fractures and a 61% reduction in multiple new vertebral fractures with denosumab, which was statistically significant compared to placebo.16,17
The efficacy of this medication compared to existing therapies is limited, due to the lack of head-to-head studies. Denosumab is expensive compared to other therapeutic options, but an advantage is biannual SC injections. Overall, denosumab serves as a therapeutic option for patients who are unable to tolerate bisphosphonates due to esophageal irritation or for patients with low levels of adherence.16,17
Estrogen/Hormone Therapy (ET/HT): Based on the NOF guidelines, ET/HT is not approved for the treatment of osteoporosis. This statement is based on the associated increased risk of stroke, pulmonary emboli, myocardial infarction, breast cancer, or deep vein phlebitis with these agents. Although FDA approved indications include prevention of osteoporosis and alleviation of symptoms associated with menopause (i.e., vasomotor symptoms, vulvovaginal atrophy), ET/HT is not recommended as a first-line agent for osteoporosis prevention.2
Future Therapies: There are several agents for the management of osteoporosis completing phase II and phase III trials that employ different mechanisms of action compared with current therapies. Odanacatib, a phase III agent, inhibits cathepsin K, which is produced by osteoclasts and functions to degrade bone.17 Two anabolic agents studied for postmenopausal women with osteoporosis, MK-5442 and AMG 785, are undergoing phase II trials that are expected to be completed in 2012. MK-5442 targets the calcium-sensing receptor (CaSR) on the parathyroid gland.17 During hypocalcemia, the CaSR is activated, causing the release of parathyroid hormone, which increases calcium levels in the blood.17 MK-5442 is known as a calcilytic drug, due to its hypocalcemic mimicking properties.17 In addition, AMG 785 is a sclerostin monoclonal antibody that functions to improve bone formation.17