What pharmacologic agents are available for use in elderly patients with low bone density?
In addition to lifestyle recommendations for all patients (adequate intake of calcium and vitamin D through the diet or supplements), several FDA-approved agents are available for management of osteoporosis and osteopenia in individuals at high risk for fractures. Bisphosphonates, antiresorptive agents that act by inhibiting osteoclast attachment to bone matrix and enhancing osteoclast apoptosis, are the first-line drug class for the improvement of bone density and fracture prevention at all major sites. For patients aged >80 years, risedronate and zoledronic acid are the only bisphosphonates to show significant reductions in new vertebral, hip, and nonvertebral fractures during a 3-year period. Possible side effects of oral bisphosphonates include dysphagia and esophagitis. Oral and intravenous bisphosphonates may impair renal function and are, thus, contraindicated in patients with an estimated glomerular filtration rate (eGFR) < 35 mL/min. There have been reports of rare but serious side effects, such as avascular necrosis, osteonecrosis of the jaw, and low-trauma atypical subtrochanteric and diaphyseal femur fractures, associated with long-term bisphosphonate use (> 3–5 years). Recommendations are to periodically reevaluate indications for continued bisphosphonate therapy, particularly in patients who have been treated for over 5 years, and to always ask about such symptoms as new thigh or groin pain.
Commonly prescribed alternatives to oral or intravenous bisphosphonates include denosumab, selective estrogen receptor modulators (SERMs), and anabolic agents.
Denosumab is a human monoclonal antibody that binds receptor activator of nuclear factor kappa-B ligand (RANKL) to prevent RANKL–RANK interaction and thereby reduces osteoclast formation and function. As an antiresorptive osteoporosis agent, it has the net effect of increasing BMD in women and men and reducing the risk of fractures (better data for fracture reduction in women). Use of denosumab could be considered in patients who have failed or are intolerant of bisphosphonates and in patients for whom bisphosphonates are contraindicated for impaired renal function. No dose adjustment is necessary in patients with renal impairment because denosumab is not renally cleared, although patients with renal disease and those with poor calcium absorption are at higher risk for hypocalcemia. Additionally, because RANKL functions within the immune system, long-term monitoring is needed to assess for an increased risk for serious infections and neoplasms. Denosumab, administered once every 6 months by subcutaneous injection, is dosed continuously without a drug holiday. Subsequent therapy with another agent is necessary if denosumab is stopped because patients are at increased risk for vertebral fractures after discontinuation of denosumab.
FDA-approved anabolic drugs include teriparatide, which is recombinant human parathyroid hormone (PTH [1-34]); and abaloparatide, which has 41% homology to PTH (1-34) and 76% homology to parathyroid hormone–related peptide (PTHrP [1-34]). These agents improve BMD and prevent fractures by stimulating osteoblast function through intermittent interaction with the PTH/PTHrP-1 receptor. They are administered via daily subcutaneous injections; this is important to consider in elderly patients who may not have the functional capacity or appropriate assistance to do so. Cumulative anabolic therapy should not exceed 2 years so it is important to evaluate the need for subsequent antiresorptive therapy.