Relationship between impaired glucose metabolism and bone mineral density in patients with cystic fibrosis

TL;DR

This study finds that impaired glucose metabolism in cystic fibrosis patients is linked to lower bone mineral density, emphasizing the need for integrated monitoring.

Contribution

The study shows that early glucose metabolism disorders, not just full-blown diabetes, are associated with reduced bone mineral density in cystic fibrosis patients.

Findings

Impaired glucose tolerance and CFRD cases had significantly lower BMI, lung function, and BMD z-scores compared to normal glucose tolerance groups.

Higher HbA1c levels were negatively associated with BMD z-scores, indicating a link between hyperglycemia and poor bone health.

HEMTs showed no significant impact on glucose or bone metabolism in this study.

Abstract

Cystic fibrosis (CF) is a chronic genetic disorder characterized by pancreatic insufficiency and lung disease. Advancements in highly effective modulator therapies (HEMTs) have improved life expectancy, shifting the focus to endocrine comorbidities, such as CF-related diabetes (CFRD) and bone disease (CFRBD). Therefore, current guidelines recommend routine screening for diabetes and osteoporosis in people with cystic fibrosis (PwCF) starting from age of 10 years. Increased risk of osteoporosis has been shown in type 1 and type 2 diabetes; however, there are limited studies evaluating the impact of glucose metabolism disorders on osteoporosis in children with cystic fibrosis. Therefore, this study investigates the impact of glucose metabolism disorders on PwCF. This cross-sectional retrospective study included 81 PwCF, aged between 10 and 21 years, who were screened routinely for diabetes and bone metabolism between 2019 and 2024. Data on demographics, CFTR variants, glucose metabolism, and biochemical bone parameters, including calcium, phosphorus, ALP, PTH, vitamin D levels with bone mineral density (BMD) of L1-L4 lumber spine were analyzed. Cases were categorized as normal, indeterminate, impaired glucose tolerance (IGT), or CFRD based on OGTT. Statistical analyses were conducted to determine factors affecting BMD, including pairwise comparison and multivariate regression analysis. Of the 81 cases, 55 (67.9%) had normal glucose tolerance, 9 (11.1%) had indeterminate (INDET), 9 (11.1%) had impaired glucose tolerance (IGT), and 8 (9.9%) had CFRD. IGT and CFRD cases demonstrated significantly lower body mass index (BMI), lung function, and BMD z-score than the normal group (p < 0.05). HbA1c had the negative association with BMD z-score (β = -0.36 per %1 increase in HbA1c, p < 0.001), while elevated BMI levels had positive relation (β = 0.28 per 1 kg/m2 increase in BMI, p = 0.009). HEMT showed no significant impact on glucose or bone metabolism, likely due to short treatment durations.

Conclusions: Impaired glucose metabolism has a significant association with BMD in PwCF. Integrated monitoring of glucose and bone metabolism, along with a multidisciplinary approach is essential to optimize outcomes and reduce complications.
What is Known:• Cystic fibrosis-related diabetes (CFRD) is the most common non-pulmonary comorbidity in CF.• Impaired glucose metabolism has been associated with reduced bone mineral density and increased fracture risk.What is New:• This study demonstrates that even early glucose metabolism disorders are associated with reduced bone mineral density in CF patients.• Higher HbA1c levels were found to be associated with lower bone mineral density, highlighting the relationship between hyperglycemia and bone health in CF.

• Cystic fibrosis-related diabetes (CFRD) is the most common non-pulmonary comorbidity in CF.

• Impaired glucose metabolism has been associated with reduced bone mineral density and increased fracture risk.

• This study demonstrates that even early glucose metabolism disorders are associated with reduced bone mineral density in CF patients.

• Higher HbA1c levels were found to be associated with lower bone mineral density, highlighting the relationship between hyperglycemia and bone health in CF.

The online version contains supplementary material available at 10.1007/s00431-025-06732-2.

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