ISPUB.COM The Internet Journal of Epidemiology Volume 7 Number 1 1 of 14 Reduction of Falls in Elderly. The central role of Alfacalcidol in a multi-dimensional paradigm E Schact, F Richy Citation E Schact, F Richy. Reduction of Falls in Elderly. The central role of Alfacalcidol in a multi-dimensional paradigm. The Internet Journal of Epidemiology. 2008 Volume 7 Number 1. Abstract Fractures in the elderly represent a major threat in terms of life expectancy and quality of life. Modern therapeutics in the fight against fractures in the elderly require pluripotent efficacy in both preserving bone mineral density and limiting falls. Indeed, epidemiological evidence has recently highlighted that agents with a targeted action on bone only may fail to prevent up to 50% of the fractures observed in patients over 60 years. Furthermore, there are growing fundamental and clinical evidences that native vitamin D is unable to reduce falls and fractures in vitamin-D replete patients and patient with deficient renal function. D- hormone analogs (Alfacalcidol and Calcitriol) have been scrutinized for two decades for their abilities to prevent BMD loss, fractures, and, more recently, falls. Alfacalcidol (1alpha (OH) D3), notably by bypassing the renal endogenous feedback loop regulation, is a synthetic vitamin D derivative with more favourable pharmacokinetic and tolerability profiles as compared to calcitriol (1,25 (OH)2 D3). Encouraging results from pilot studies have driven research, and led to modern data able to support a pseudo Copernician change by switching from supplementation with vitamin D to actively treat bone, muscle, and neurocoordination with Alfacalcidol. This systematic narrative review browses the current pilot, clinical and meta-analytical data to demonstrate, in an evidence-based fashion, that the D-Hormone analog Alfacalcidol is an excellent candidate in preventing falls and fractures to a greater extent as compared to native vitamin D. The continuum of evidence synthesized in this paper highlights the necessary change in medical paradigm to efficiently prevent fractures in the elderly, and opens new research pathways, notably in combination therapies with Alfacalcidol. AGE-RELATED FRACTURES; A MULTIFACTORIAL PARADIGM Clinical experience and epidemiological data demonstrate that mobility and balance are key determinants of improved quality of life in worldwide aging populations. Falls currently tends to be a primary outcome in clinical trials given their consequences, in terms of fractures, quality of life and psychological consequences, including deconditioning and kinesophobia. A significant number of osteoporotic fractures are associated with falls, independently of bone mineral density (BMD) 1 . Fractures are of the most conservative outcome in the fight against osteoporosis. Recently it was shown that 54% of women aged 65 years or older with incident hip fractures were not osteoporotic 2 . Established osteoporosis in older patients of both sexes is characterized by decoupled bone remodelling induced by a deficit in sex hormones, as well as by a somatopause (insulin-like growth factor [IGF]-deficit), but also by a lack of circulating vitamin D, a reduced synthesis of D-Hormone in the kidneys and bones and by a lack of receptors and/or receptor affinity for D-Hormone (VDR’s) in the target organs leading to increased parathormone (PTH) levels and a higher bone turnover 3 . In parallel to decreased bone strength, a loss of muscle power and performance (sarcopenia), neuromuscular deficiencies, deterioration in gait and postural stability appears in the age of 65-70 years in both genders and are very common. These deficiencies, together with slower response times lead to an increase of intrinsic, non-syncopal, locomotoric falls with no or only minimal contributions of external obstacles during normal daily activities. Together with a higher incidence of bone loss, differences in the types of falls, more often sideways instead of forward, and therefore, the direct impact of force on the hip together with the loss of soft tissue covering also explain the increased in hip fractures in elderly people over the age of 75. There is a current consensus that the combination of reduced bone strength and increased fall risk account for most of the variability for the different types of age-, fall- and osteoporosis-related peripheral, and, to a lesser extent,