British Journal of Clinical Pharmacology | 2019
Drugs for the treatment of metabolic bone diseases
Abstract
Musculoskeletal conditions comprise more than 150 diagnoses that affect the locomotor system—that is, muscles, bones, joints, and associated tissues such as tendons and ligaments. Musculoskeletal conditions are the second largest contributor to disability worldwide. Among them, bone diseases constitute a significant health burden, although often overlooked by care providers and patients alike. Quantitatively, osteoporosis is the most important metabolic bone disease, with roughly 50% of women and 20% of men greater than 50 years of age expected to suffer an osteoporosis‐associated fracture during their remaining lifetime. In Europe, this translates into annualized rates of 574 000 wrist, 810 000 spine, and 620 000 hip fractures. Collectively, these osteoporotic fractures result in substantial numbers of hospitalizations and increases in mortality, ultimately leading to an estimated annual overall cost of 37 Billion Euro. Similar numbers have been described for the United States. With fracture incidence on the rise due to aging of the world s population, osteoporosis is rightfully referred to as a silent epidemic. In comparison, rare metabolic bone diseases such as fibrodysplasia ossificans progressiva (or FOP) can also exert significant burdens on our collective public health systems, a result reflecting the skeletal severity of such diseases rather than the number of patients affected. A third category of diseases involving the skeleton are cancer‐associated bone diseases, comprising disorders of both bone loss and bone metastases, which again affect large numbers of patients. Over the past several decades, new drugs have become available for the treatment of various metabolic bone diseases, including Paget s disease of bone, osteoporosis, and metastatic bone disease. Indeed, 2019 will mark 50 years since the first publications on the biological effects of the bisphosphonates, a therapeutic class that has been dominating the treatment of Paget s disease of bone, osteoporosis, cancer‐associated bone disease, and several rare bone diseases such as osteogenesis imperfecta for years. In this themed issue, one of us who has been involved from the very inception of early bisphosphonate research (RGR) discusses the clinical and translational pharmacology of these drugs, as well as their continued development for the treatment of metabolic bone diseases. Despite their widespread clinical utility, however, bisphosphonate use has declined over the past decade. Reasons for this decline are several and include patient and provider concern for rare side effects associated with their long‐term use as described by Skjødt et al, loss of patent protection, and decreased reimbursement for bone mineral density (BMD) testing by dual‐energy X‐ray absorptiometry (DXA) in