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IOF World Congress Abstracts Fall prevention – as important as maintaining bone mass
in preventing osteoporotic bone fractures The pathophysiology of osteoporosis and of resulting bone fractures is complex and multifactorial, enabling various potential sites of intervention. While traditional osteoporosis therapeutics typically address either the prevention of bone loss or the generation of new bone mass, researchers are targeting a novel approach that also addresses an important, albeit often ignored underlying factor contributing to osteoporotic bone fractures: the use of pharmacological substances that help to prevent falls by improving postural stance, gait and muscular strength. While osteoporosis is an important factor contributing to bone fractures, the increased propensity to fall is no less important and increases with advancing age. Vitamin D deficiency, together with the abnormal synthesis and/or activity of the D-hormone alfacalcidol, contribute to poor calcium absorption, increased levels of parathyroid hormone (PTH), decoupled bone remodeling and reduced muscle strength. Older women and men have slower response times and more often fall to the side, suffering direct impacts to the hip. Furthermore their falls are often "intrinsic", or unrelated to external obstacles, resulting from deterioration in gait and postural instability, decreased muscular performance, malnutrition, comorbidity (e.g., poor vision, cognitive impairment) and medications. The importance of muscle strength and coordination, which typically decline in the later years of life, as factors contributing to falls that result in bone fractures should not be overlooked. Vitamin D analogues, or D-hormone analogues, have well-known effects on skeletal muscle cells, improving muscle function and balance as well as increasing bone volume and inhibiting bone resorption. These characteristics make them an attractive alternative in the treatment of elderly patients with osteoporosis, independent of vitamin D status. Studies using the vitamin D analogue calcitriol, the D-hormone prodrug alfacalcidol and the second-generation D-hormone analogue ED-71 indicate that these dual effects – improved bone quality and reduction in the frequency of falls – translate into clinical benefit for elderly osteoporotic patients. The STOPIT study, a double-blind, randomized study involving nearly 500 elderly Caucasian women (age 71 years), compared the effects of calcitriol (0.25 mcg b.i.d.) with those of hormone replacement therapy (conjugated equine estrogens 0.625 mg + MPA 2.5 mg), the two in combination, or placebo, for a period of more than three years. Women in the study, none of whom showed signs of vitamin D deficiency, all had significant increases in bone mineral density (BMD) of the spine with active treatment. Although the effects of calcitriol on BMD were less pronounced than those of HRT (+1.8% vs. +5.7%, respectively), women in the calcitriol treatment group suffered 36% fewer falls than those in the HRT group. The significance of fall reduction in preventing osteoporotic fractures should not be underestimated, according to lead investigator Dr. J.C. Gallagher, and a drug that both improves bone quality and reduces falls is of strong therapeutic value.
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