Osteoanabolic Agents for Osteoporosis

Andrea V. Haas; Meryl S. LeBoff

Disclosures

J Endo Soc. 2018;2(8):922-932. 

In This Article

Abstract and Introduction

Abstract

Medications for osteoporosis are classified as either antiresorptive or anabolic. Whereas antiresorptive agents prevent bone resorption, anabolic agents promote new bone formation. Anabolics should be considered in individuals with severe osteoporosis, failure of alternative osteoporosis agents, intolerability or contraindications to other osteoporosis agents, and glucocorticoid-induced osteoporosis. There are currently two approved anabolic therapies, teriparatide and abaloparatide, and a third anabolic agent, romozosumab, is under review by the US Food and Drug Administration. Teriparatide and abaloparatide are administered as daily subcutaneous injections and have been shown to reduce vertebral and nonvertebral fractures significantly. The most common side effects are headache and nausea, but teriparatide and abaloparatide are generally well tolerated. The sequence of administration of anabolic therapy is important. Benefits of anabolics are attenuated in individuals with prior antiresorptive exposure; however, antiresorptive agents administered after anabolics consolidate bone mineral density gains.

Introduction

Osteoporosis is a major and growing public health concern. Approximately one in two women and one in five men, aged 50 and older, will experience an osteoporotic fracture.[1] Fractures are associated with reduced independence, increased risk of future fractures, and increased morbidity and mortality.[2,3] Effective prevention and treatment of osteoporosis and fractures are of paramount importance.

The overarching goal of treating osteoporotic patients is to prevent incidence of fractures. Osteoporosis treatment is achieved through either inhibition of bone resorption and/or stimulation of bone formation. To date, antiresorptive agents (e.g., bisphosphonates, denosumab, estrogen, and raloxifene) are the most commonly used therapies for the treatment of osteoporosis. Through diverse mechanisms, antiresorptive agents suppress osteoclastic-mediated bone breakdown and bone turnover.[4] Conversely, osteoanabolic agents promote new bone formation by activation of osteoblasts and bone remodeling.[5]

Teriparatide and abaloparatide are currently the only two approved anabolic agents for the treatment of osteoporosis in the United States. The US Food and Drug Administration (FDA) approved teriparatide in 2002 and abaloparatide in 2017. Both agents reduce the incidence of vertebral and nonvertebral fractures.[6,7] A third agent, romosozumab, has remained under evaluation by the FDA, given concerns regarding increased cardiovascular events.[8]

The aims of this review are to discuss the mechanism of action, clinical use, and major clinical studies of anabolic drugs for the treatment of osteoporosis. Relevant studies were selected after a PubMed search through December 2017 and included at least one of the following keywords: anabolic, bone mineral density (BMD), fracture, teriparatide, abaloparatide, and romosozumab. Articles of potential interest were then reviewed in full. Additional articles were identified from those publications' references.

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