Formulary Update on Osteoporosis in Men and Postmenopausal Women

The treatment for Osteoporosis is a constantly evolving field. Since diagnosis often occurs after a fragility fracture, early treatment focuses on fracture management. However, more and more emphasis is being placed on prevention and early detection. Bisphosphonates changed the management of the disease, but they presented new problems like atypical proximal femur fractures. The current recommendation for patients on long-term bisphosphonates is a drug holiday after 5 years for oral use, and 3 years after intravenous use. While bisphosphonates remain the gold standard, other medications have improved our ability to combat the disease, like Forteo (teriparatide; Eli Lilly). Prevention using supplementation like calcium and Vitamin D has also been beneficial, but has recently come under fire with certain publications linking calcium to cardiovascular disease. However, recent recommendations still advocate their use.  

Fracture liaison services and orthogeriatric services have started to improve post-fragility fracture management of osteoporosis and future fracture prevention. While the effectiveness of these services has been inconclusive, most data supports their use—they are cost-effective, likely improve mortality, aid in patient understanding, and improve patient care. Screening patients has also improved, with FRAX and DXA scans allowing for earlier diagnosis and treatment. Several recommendations on current testing guidelines are available.

Considerations in Men

Studies investigating osteoporosis in men have lagged behind the plethora of information available regarding women, despite it being a leading cause of morbidity and mortality in elderly men. The screening age for men is higher, with most authorities recommending bone mineral density (BMD) testing in men over 70. Of note, testosterone levels are inversely proportional to fracture risk, so men who are at risk for testosterone deficiency (eg prostate ablation) should be monitored closely. However, the use of testosterone supplementation has limited efficacy and has only been shown to improve BMD and not prevent secondary fractures. Unfortunately, there are fewer medications available that have been studied, or approved, for use in men. Even recent recommendations from the American College of Physicians for the use of bisphospohates in men are based on limited evidence. A recent meta-analysis has shown that bisphosphonates are advantageous, but have only proven to prevent secondary vertebral fractures (zoledronic acid, and possibly alendronate). New generation bisphosphonates and Prolia (Denosumab; Amgen) have shown to increase BMD in men. However, Prolia only has approval from the FDA in men who are at a high risk for fracture and receiving androgen deprivation therapy for nonmetastatic prostate cancer. Even Forteo is only approved for severe osteoporosis in men. This leaves the current recommendations surrounding the treatment of men mostly with vitamin D/calcium and bisphosphonates. However, this is likely a result of a lack of evidence and not a lack of efficacy of the drugs themselves. More studies surrounding men and the treatment/management of osteoporosis in men are needed, especially those focusing on secondary fracture prevention.

Considerations in Postmenopausal Women

More extensively studied, the current recommendations and treatment methods for women is stronger. Current recommendations for screening in the normal population is aged 65 and older. Newer medications, like Forteo and Prolia have provided an alternative to bisphosphonates, and even as treatment adjuncts for bispohsophonate-related atypical femur fractures. However, these medications can be expensive, with Forteo currently costing over $3000 for a 4 week supply. Daily injections are limited to 2 years and is contraindicated in patients with Paget diease. Forteo prevents both vertebral and nonvertebral fractures in postemenopausal women. 

Tymlos, (Abaloparatide; Radius) a new parathyroid hormone type 1 receptor activator, recently completed phase 3 clinical trials and was shown to be more effective than Forteo in the prevention of new osteoporotic fractures. Tymlos recently received FDA-approval for use among post-menopausal women. 

Prolia was also approved in 2010 by the FDA for treatment of postmenopausal osteoporosis. Prolia has been shown to decrease both vertebral, and non-vertebral fractures in postmenopausal women. It has also been shown to have a higher compliance rate than bisphosphonates—it’s a biannual injection. It costs approximately $1100 per treatment, but the yearly cost is still relatively low when compared to alternatives. However, Prolia has been linked to higher rates of infection and side effects previously thought to be unique to bisphosphonates, including osteonecrosis of the jaw and possibly atypical femur fractures. Selective Estrogen Receptor Modulators (SERMs) have also been studied in this subset of patients. While SERMs are not necessarily new, a newer medication Bazedoxifene, along with Duavee (conjugated estrogens; Pfizer) has been approved by the FDA for prevention (not treatment) of osteoporosis and has been shown to prevent both vertebral and nonvertebral fractures. However, the risks associated with the use of unopposed estrogens remain, including endometrial cancer, and the recommendation is to use only in severe cases and limited duration. Many options are available to postmenopausal women, and treatment should be tailored to the individual. 

Fracture Liaison/Orthogeriatric Services

Ubiquitous to all patients with osteoporosis, a focus on inpatient/outpatient care is important. The recognition after fragility fracture, initiation of treatment, and follow up on treatment is important. Fracture Liaison Services and Orthogeriatric Services are becoming increasingly important tools in the treatment and management of osteoporosis, particularly after fragility fracture. One of the key points of these services is to ensure collaboration between specialty practices and the patient’s primary care team, which has traditionally been poor. Although the exact model varies, these services are cost-effective, and decrease secondary fracture risk and mortality. The implementation of these types of services should be a key focus for osteoporosis management and prevention in any practice setting.