Correction of the Gene Defect in Cystic Fibrosis: Is It Too Late for Bone?

Tangpricha, Vin

doi:10.1210/clinem/dgab074

Cited by 2 publications

(4 citation statements)

References 7 publications

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“…71 In addition to potential direct effects of restoring CFTR function on bone health, indirect benefits may include improved absorption of vitamin D from the gastrointestinal tract, 72 increased exercise capacity, improved nutritional state, and reduced infection and inflammation. 73 Together, these early findings are encouraging and, given the tolerability and safety of modulator therapies, clinical improvements in cystic fibrosisrelated bone disease should be anticipated. However, optimal clinical management for adults receiving modulator therapy with declining bone mineral density and/or osteoporotic fracture remains unclear, and research is needed to clarify whether adjunct use with currently available bone preservation therapies is safe and efficacious.…”

Section: Effects Of Modulators On Cystic Fibrosis-related Bone Diseasementioning

confidence: 93%

“…A pilot study demonstrated that weight gain improved bone mineral density and exercise capacity in nine individuals with cystic fibrosis (mean age, 18.6 years; standard deviation, 4.7 years) who were administered ETI compared with cystic fibrosis controls 71 . In addition to potential direct effects of restoring CFTR function on bone health, indirect benefits may include improved absorption of vitamin D from the gastrointestinal tract, 72 increased exercise capacity, improved nutritional state, and reduced infection and inflammation 73 . Together, these early findings are encouraging and, given the tolerability and safety of modulator therapies, clinical improvements in cystic fibrosis‐related bone disease should be anticipated.…”

Section: Cystic Fibrosis‐related Bone Diseasementioning

confidence: 99%

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Effects of modulator therapies on endocrine complications in adults with cystic fibrosis: a narrative review

Kumar,

Soldatos,

Teede

et al. 2023

Medical Journal of Australia

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Summary Cystic fibrosis is a monogenic disorder caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) protein, which transports chloride ions in secretory organs. Modulator therapies are small molecules that correct CFTR dysfunction and can lead to a wide range of benefits for both pulmonary and extrapulmonary complications of cystic fibrosis. With advancements in airway, antimicrobial and nutritional therapies and now introduction of modulator therapies, most people living with cystic fibrosis in Australia are now adults. For adults with cystic fibrosis, endocrine manifestations such as cystic fibrosis‐related diabetes, metabolic bone disease, and reproductive health are becoming increasingly important, and emerging evidence on the endocrine effects of CFTR modulator therapies is promising and is shifting paradigms in our understanding and management of these conditions. The management of cystic fibrosis‐related diabetes will likely need to pivot for high responders to modulator therapy with dietary adaptions and potential use of medications traditionally reserved for adults with type 2 diabetes, but evidence to support changing clinical care needs is currently lacking. Increased attention to diabetes‐related complications screening will also be required. Increased exercise capacity due to improved lung function, nutrition and potentially direct modulator effect may have a positive impact on cystic fibrosis‐related bone disease, but supporting evidence to date is limited. Fertility can improve in women with cystic fibrosis taking modulator therapy. This has important implications for pregnancy and lactation, but evidence is lacking to guide pre‐conception and antenatal management. Provision of multidisciplinary clinical care remains ever‐important to ensure the emergence of endocrine and metabolic complications are optimised in adults with cystic fibrosis.

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Section: Effects Of Modulators On Cystic Fibrosis-related Bone Diseasementioning

confidence: 93%

Section: Cystic Fibrosis‐related Bone Diseasementioning

confidence: 99%

Effects of modulator therapies on endocrine complications in adults with cystic fibrosis: a narrative review

Kumar,

Soldatos,

Teede

et al. 2023

Medical Journal of Australia

View full text Add to dashboard Cite

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“…CFTR modulator therapies may improve bone density by targeting dysfunctional CFTR in the bone or by ameliorating other risk factors for CF bone disease [86] . CFTR is expressed in human osteoblasts and CFTR-deficient cells demonstrate increased RANK-L:OPG ratio and reduced prostaglandin E-2 (PGE-2) levels, suggesting tissue-level alteration in bone modeling pathways [87] .…”

Section: Pharmacologic Therapymentioning

confidence: 99%

“…Importantly, application of the C18 corrector to cultured osteoblasts increased RANK-L and PGE-2, suggesting that CFTR modulator therapy may directly treat low BMD in people with CF [88] . CFTR modulator therapy may also indirectly improve bone health by improving nutrient absorption, hypogonadism, and pulmonary disease [86] . Clinical studies of Ivacaftor in adults with CF with at least one copy of the G511D mutation suggest some impact on BMD.…”

Section: Pharmacologic Therapymentioning

confidence: 99%

Treatment of cystic fibrosis related bone disease

Ullal

Kutney

Williams

et al. 2022

Journal of Clinical & Translational Endocrinology

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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.

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Correction of the Gene Defect in Cystic Fibrosis: Is It Too Late for Bone?

Cited by 2 publications

References 7 publications

Effects of modulator therapies on endocrine complications in adults with cystic fibrosis: a narrative review

Effects of modulator therapies on endocrine complications in adults with cystic fibrosis: a narrative review

Treatment of cystic fibrosis related bone disease

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