Safety of drugs used in the treatment of osteoporosis

Abstract

A number of drug classes are licensed for the treatment of osteoporosis including bisphosphonates, recombinant human parathyroid hormone (PTH), strontium, hormone replacement therapy (HRT), selective oestrogen receptor modulators (SERMS) and denosumab. This review discusses the safety of osteoporosis treatments and their efficacies. Recent concerns about the safety of calcium and high-dose vitamin D are discussed. Bisphosphonates have substantial postmarketing experience and a clearer picture of safety issues is emerging. Along with the well recognized effects on the gastrointestinal tract and kidney function, recently described adverse effects such as osteonecrosis of the jaw, oesophageal cancer, atrial fibrillation, subtrochanteric femur fractures and ocular complications of bisphosphonate therapy are discussed. Therapy with PTH is limited to two years' duration because of the development of osteogenic sarcomas in animal studies, which appeared related to dose, duration and timing of therapy. Strontium should be used with caution in patients with renal impairment and its use has been associated with venous thromboembolism. The role of HRT and SERMs in the treatment of postmenopausal osteoporosis is restricted as a result of an increased risk of stroke, venous thromboembolism and breast cancer. Postmarketing experience with denusomab is limited but a number of potential safety concerns including osteonecrosis of the jaw are emerging. All of these drugs have been proven to reduce fractures. The decision to use a drug to reduce fracture risk should be based on risk-benefit analysis of the drug and its suitability for individual patients.

Bibliographic review on the state of the art of strontium and zinc based regenerative therapies. Recent developments and clinical applications

“…Current evidence affirms that strontium ranelate mediates an uncoupling in bone turnover since it enhances osteogenesis and osteoblast activity while decreasing osteoclast differentiation and function; 116 but also that it has serious side effects such as memory loss or increased risk of venous thromboembolism. 15 However, new investigations substituting ranelic acid for vitamin-B derivatives of Sr or Zn are being recently described with very promising characteristics. 117 Biocompatibility is crucial in terms of regenerative therapies; most of the studies were carried out using Zn and/or Sr doped scaffolds (bioactive glasses, nanofibers.…”

“…14 The current therapies used for osteoporosis include: vitamin D and calcium supplements, bisphosphonates, teriparatide (TPH), hormone replacement therapy, selective oestrogen receptor modulators (SERMs), RANK ligand inhibitors and strontium ranelate, in which the safety issues and side effects are quite concerning. 15 Regenerative therapies imply the replacement or regeneration of human cells, tissues or organs with the purpose of returning the patient to full health, 16 by using concrete factors to upgrade the natural healing potential. 17 Currently there are still many diseases with no effective medical therapy which could be treated with tissue replacement.…”

A network meta‐analysis on the short‐term efficacy and adverse events of different anti‐osteoporosis drugs for the treatment of postmenopausal osteoporosis

“…Risedronate, a novel orally administered pyridinyl bisphosphonate prescribed for the prevention or treatment of postmenopausal and glucocorticoid‐induced osteoporosis and Paget's disease, can reduce bone turnover and decreases resorption chiefly through osteoclastic effects, with no undesirable effects on cortical porosity or thickness or on cancellous bone volume . However, gastrointestinal (GI) effects of oral bisphosphonates are well observed and recognized and vary from mild nausea and heartburn to erosive oesophagitis and ulceration . Prolonged treatment with alendronate has been associated with adynamic bone disease and atypical long bone fractures in postmenopausal osteoporosis .…”

Inhaled Corticosteroids and Bone Health

“…The risk-benefit ratio currently favours the use of bisphosphonates in the prevention of osteoporotic fractures from GIO. Cumulative toxicity occurs with renal impairment and these drugs should be avoided when glomerular filtration rate falls below 30 ml/minute [ 61 ]. Poor adherence to treatment is an important issue with bisphosphonate treatment and annual supervised intravenous therapy with the long-acting agent zoledronic acid may largely resolve this issue.…”