Medical Therapy for Osteoporosis and Approaches to Improving Adherence

Deficiency of vitamin D is common with one study finding more than 90% of older adults deficient in vitamin D [10]. Vitamin D is essential for proper calcium metabolism and deficiency is known to induce secondary hyperparathyroidism. Studies in mouse models have also shown that normal vitamin D receptors in enterocytes are essential for normal bone mineralization [11,12]. A systematic Cochrane database review showed that vitamin D3 supplementation decreased mortality in elderly people living independently or in institutional care [13]. Vitamin D was administered for a weighted mean of 4.4 years. Vitamin D2, alfacalcidol, and calcitriol had no statistically significant beneficial effects on mortality. Vitamin D3 combined with calcium was associated with an increased risk of nephrolithiasis during a follow-up period of 1.25 to 7 years (relative risk [RR] 1.17, 95% confidence interval (CI) 1.02–1.34) [13]. The inconsistencies of published reports looking at benefits of vitamin D supplementation may be due in part to variability in compliance with taking the supplements and baseline vitamin D levels.

Two randomized controlled trials have shown that low vitamin D appears to be an independent predictor of fall risk, and vitamin D supplementation has been found to reduce this risk of falls, through improved musculo-skeletal function [14–16]. Thus, vitamin D may play a role in fracture risk reduction beyond direct bone effects.

Prescription Osteoporosis Treatments

Bisphosphonates

Bisphosphonates are the most commonly prescribed medication for osteoporosis. The efficacy of bisphosphonates to reduce fractures is well established. There are oral bisphosphonates, which can be dosed daily, weekly, or monthly, and intravenous bisphosphonates, which can be given every 3 months or annually. Side effects with this class of medications include gastrointestinal effects with the oral options in up to 20% to 30% of users [17]. With intravenous bisphosphonates, the greatest risk is an acute phase response, which can occur in up to 42% of patients [18]. The risk of an acute phase reaction is much lower with doses beyond the first dose and lower if patients have ever previously taken an oral bisphosphonate and/or receive acetaminophen prior to the infusion. Other potential side effects with all bisphosphonates include osteonecrosis of jaw (ONJ) and atypical subtrochanteric fractures. Post marketing studies have indicated that the incidence of ONJ is less than 2 per 100,000 patient-years among those taking bisphosphonates [19,20]. A number of database analyses have shown that ONJ-like lesions can also occur in older individuals with osteoporosis who have never been exposed to bisphosphonates [21]. A case series of an osteoporotic population showed that ONJ-like lesions are lower grade than those typically seen in cancer patients who usually are exposed to higher doses of bisphosphonates [22]. A study of Swedish older men and women reported that long-term use of bisphosphonates (4 years or more) was associated with an increased incidence of atypical fractures. The RR for women was 126.0 (95% CI, 55.1–288.1) after 4 years of bisphosphonates [23]. A U.S. health care database analysis reported that 90% of those with atypical fractures were bisphosphonate users, almost half were Asian (49%), and use beyond 6 years showed the greatest risk [24].