Cellular and Animal Models for the Identification of Osteoporosis Determinants Increasing Vertebral Compression Fractures Risk

Abstract

The increase in lifespan in western society has led to a consequent increase of osteoporosis substantially decreasing quality of life and increasing healthcare costs and the need for additional therapeutic strategies. Even obesity, a major health issue in industrialized countries, has recently been associated to deteriorated bone microarchitecture and increased prevalence of vertebral fractures [8]. Currently approved therapeutic options to treat osteoporosis are several and include the estrogen replacement therapy, the use of selective estrogen receptor modulators (SERMs) such as raloxifene, the bisphosphonates (e.g., alendronate, risedronate, ibandronate, and zoledronic acid), calcitonin, recombinant human parathyroid hormone (rhPTH) and its derivatives (e.g., teriparatide), the monoclonal antibody denosumab that binds the receptor activator of nuclear factor κ-B ligand (RANKL), and strontium ranelate (not approved in the United States) [9,10]. However, there are particularly challenging categories of osteoporotic patients that show an inadequate response to therapy and patients with pre-existing conditions, such as renal or gastrointestinal diseases, that may not tolerate the existing therapies [11]. Indeed, most of the drugs currently available present contraindications and even severe side effects. For example, biphosphonates, that represent often the first-choice therapy for osteoporosis, although effective in reducing bone loss and vertebral

Experimental Modeling of Osteoporosis in Animals

“…The methods used to assess the bone mass, architecture and bone turnover in animals with a modelled osteopenia and osteoporosis are similar to the ones used for similar purposes in humans, though in animals this range is much wider [1,19]. Both in animals and humans, one measures the biochemical marker rates in blood and urine, i.e.…”

“…for an initial assessment of new osteoporosis medications. The mice require fewer medications; their osteoporosis develops quickly and has some characteristic features [19].…”

Sheep Gait Biomechanics and the Assessment of Musculoskeletal Conditions: A Systematic Review

“…Thus, to assess the effect of a treatment in sheep with osteoporosis, most of the studies conducted in other animals, use parameters related with bones properties, essential to measure bone mineral density and diagnosis osteoporosis, but this only give us information about the bone structure and does not evaluate the functional impairment [5,6]. Due to this limitation, and since sheep have been identified as ideal for studies related to osteoporosis [4], it´s important to identify functional biomechanical outcome measures that could also be used to assess the effects of new therapies on these animals, similar to completed studies with rats [7][8][9][10][11].…”