New horizons in treatment of osteoporosis

Abstract

Background: Prevalence of osteoporosis is increasing both in developed and developing countries. Due to rapid growth in the burden and cost of osteoporosis, worldwide, it seems reasonable to focus on the reduction of fractures as the main goal of treatment. Although, efficient pharmacological agents are available for the treatment of osteoporosis, there still remains a need to more specific drugs with less adverse effects.

Main body: This review article provides a brief update on the pathogenesis, presenting current pharmacological products approved by the US Food and Drug Administration (FDA) or Europe, and also newer therapeutic agents to treat osteoporosis according to the clinical trial data available at PubMed, UpToDate, International Osteoporosis Foundation (IOF), and clinical practice guidelines. As well, the effect of combination therapy and recommendations for future research will be further discussed.

Short conclusion: The use of current antiresorptive and anabolic agents alone or in combinations for the treatment of osteoporosis entails several limitations. Mainly, their efficacy on non-vertebral fracture reduction is lower than that observed on vertebral fracture. In addition, they have potential adverse events on long time usage. Development of newer agents such as cathepsin k inhibitor and strontium ranelate not only have increased the available options for treating osteoporosis, but also have opened doors of opportunity to improvements in the effective treatment. However, the high cost of new agents have restricted their usage in selective patients who are at high risk of fracture or whom failed response to first line treatment options. Thus, personalized medicine should be considered for future evaluation of genetic risk score and also for environmental exposure assessment. In addition to permanent attention to early diagnosis of osteoporosis and understanding of the pathophysiology of osteoporosis for novel approach in drug discovery, there seems a need to more well-designed clinical trials with larger sample sizes and longer duration on current as well as on newer agents. Also, continuous research on plant-derived components as the source of discovering new agents, and conducting more clinical trials with combination of two or more synthetic drugs, plants, or drug-plant for the treatment of osteoporosis are recommended. Summary of treatment modalities for osteoporosis.

Keywords: Anabolic agents; Antiresorptive; Fractures; Osteoporosis; Personalized medicine; Plants; Treatment.

Fig. 1

A brief schematic view of pathophysiology of osteoporosis and influence of some drugs on bone health. Legend: PTH: parathyroid hormone; PGE2: prostaglandin E2; IL-11: interleukin-11; OPG: osteoprotegerin; OCIF: osteoclastogenesis inhibitory factor; RANKL: receptor activator of nuclear factor κB ligand; NF-κB: nuclear factor κB; JNK: c-Jun N-terminal kinases; OCs: osteoclasts; Wnt: wingless and Int proteins; LRP5/6: LDL-receptor related protein 5/6; IGF-1: Insulin like growth factor-1; L-C: L-carnitine; OBs: osteoblasts