Pharmaceutical management of bone catabolism: the bisphosphonates

Ej Raubenheimer,Lb Lemmer,Hd Miniggio,Cee Noffke,T Slavik,Wfp Van Heerden

doi:10.17159/2309-8309/2019/v18n1a6

Abstract

Background: Conditions associated with catabolism of bone are common and progress sub-clinically with devastating skeletal consequences. Over the past two decades, bisphosphonates have become increasingly popular for the preventative management of the skeleton in these conditions. Methods: Recent literature pertaining to the mechanisms of action, clinical indications and complications of bisphosphonate therapy was retrieved using Google Scholar and Pubmed. Aims of study: To provide an overview of the mechanisms of action, indications, contraindications and complications of the bisphosphonates available for clinical use in South Africa. Results: Despite the availability of alternative management regimens, bisphosphonates remain the pharmaceuticals of choice for the management of hypercalcaemia and generalised catabolic skeletal disorders such as osteoporosis, skeletal metastatic disease, Paget’s disease of bone, glucocorticoid bone disease and osteogenesis imperfecta. Although adverse complications such as tachycardia, bowel and oesophageal irritation, pain, jawbone necrosis and atypical femur fractures are well documented, information remains limited on the long-term effects of bisphosphonate therapy on skeletal health. This manuscript provides an update on the mechanisms of action, principles applied to the selection of the most appropriate management regimen, monitoring of the response and complications of the bisphosphonates marketed in South Africa. Level of evidence: Level 5

Highlights

Despite the development of innovative pharmaceuticals and autoantibodies for the manipulation of skeletal metabolism, bisphosphonates (BPs) remain the first-line choice for the management of hypercalcaemia and several systemic catabolic skeletal disease states
The incorporated BPs are released where they exert a profound local influence on the cellular components of the bone metabolic unit (BMU) and in particular the osteoclasts
In a consensus statement of the Mayo Clinic Myeloma Group, IV pamidronate is recommended as the drug of choice for the management of these morbidities as pamidronate effectively suspends bone resorption, alleviates bone pain and corrects hypercalcaemia

Summary

Introduction

Despite the development of innovative pharmaceuticals and autoantibodies for the manipulation of skeletal metabolism (reviewed elsewhere1), bisphosphonates (BPs) remain the first-line choice for the management of hypercalcaemia and several systemic catabolic skeletal disease states. An acute phase reaction is experienced by nearly a quarter of patients receiving the first IV dose of nitrogen-containing BP, and the incidence thereafter decreases progressively with each administration.[44] This reaction is characterised by pyrexia with concomitant headache, arthralgia, myalgia and influenza-like symptoms, and pre-treatment with histamine receptor antagonists, antipyretics or corticosteroids may provide relief.[1] An increase in serious atrial fibrillation (requiring hospitalisation) was reported in patients receiving IV zoledronic acid.[44] verifiable data is not yet available for the other BPs, the risk appears to be smaller, if not negligible.[7] This complication is an indication for considering one of the non-BP skeletal cytokine modulators or auto-antibodies in the management regimen (summarised elsewhere[1]). Administration of BPs is contraindicated during pregnancy, lactation and in patients manifesting with allergic-type reactions against the drug

Conclusion

Findings

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