Treatment of cystic fibrosis related bone disease

Jagdeesh Ullal, Katherine Kutney, Kristen M Williams, David R Weber, Jagdeesh Ullal, Katherine Kutney, Kristen M Williams, David R Weber

Abstract

The advent of highly effective CFTR modulator therapies has slowed the progression of pulmonary complications in people with cystic fibrosis. There is increased interest in cystic fibrosis bone disease (CFBD) due to the increasing longevity of people with cystic fibrosis. CFBD is a complex and multifactorial disease. CFBD is a result of hypomineralized bone leading to poor strength, structure and quality leading to susceptibility to fractures. The development of CFBD spans different age groups. The management must be tailored to each group with nuance and based on available guidelines while balancing therapeutic benefits to risks of long-term use of bone-active medication. For now, the mainstay of treatment includes bisphosphonates. However, the long-term effects of bisphosphonate treatment in people with CF are not fully understood. We describe newer agents available for osteoporosis treatment. Still, the lack of data behooves trials of monoclonal antibodies treatments such as Denosumab and Romozosumab and anabolic bone therapy such as teriparatide and Abaloparatide. In this review, we also summarize screening and non-pharmacologic treatment of CFBD and describe the various options available for the pharmacotherapy of CFBD. We address the prospect of CFTR modulators on bone health while awaiting long-term trials to describe the effects of these medications on bone health.

Keywords: Bisphosphonates; Bone density; Bone density screening; Cystic fibrosis; Cystic fibrosis bone disease.

Conflict of interest statement

Conflict of Interest or Competing Interest: My coauthors and I do not have any conflict of interest other than the fact that 3 of us were funded by the Cystic Fibrosis Foundation. A Declaration of Interest: there is no financial/personal interest or belief that could affect our objectivity, and there is no potential competing interests.

© 2021 The Authors.

Figures

Fig. 1
Fig. 1
Cystic Fibrosis bone disease (CFBD) is a multifactorial problem that necessitates a multipronged approach to treatment and mitigation. The figure below highlights the major factors that contribute to the pathogenesis of CFBD (shown in boxes) and the appropriate mitigation strategy (shown with arrows) that should be considered along with pharmaceutical therapy if indicated. (Abbreviations: PERT, pancreatic enzyme replacement therapy; CFTR, Cystic Fibrosis Transmembrane Conductance Regulator; GH, Growth Hormone; IGF-1, insulin-like growth factor-1; CFRD, cystic fibrosis related diabetes).

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