Genotyping Predicts Osteoporosis Risk after Lung Transplantation
Lung transplant recipients have the highest rates of osteoporosis and fragility fractures of any solid organ transplant population. Several single nucleotide polymorphisms in genes important for bone metabolism have been identified. We hypothesized that risk alleles in these genes would be associate...
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| Published in: | The Journal of heart and lung transplantation Vol. 39; no. 4; p. S194 |
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| Main Authors: | , , , , , , , , , |
| Format: | Journal Article |
| Language: | English |
| Published: |
United States
Elsevier Inc
01-04-2020
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| Online Access: | Get full text |
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| Summary: | Lung transplant recipients have the highest rates of osteoporosis and fragility fractures of any solid organ transplant population. Several single nucleotide polymorphisms in genes important for bone metabolism have been identified. We hypothesized that risk alleles in these genes would be associated with decreased bone mineral density (BMD) following lung transplantation.
Between 2002 and 2018, 114 lung transplant recipients were genotyped at 18 loci important for bone health. Bisphosphenates, calcium, and vitamin D were given per protocol. Subject data including baseline characteristics and pre- and post- transplant bone densitometry scores were abstracted from medical records. Changes in t-scores at the hip, femoral neck, and lumbar spine were calculated over time using linear models. Associations between density t-score slopes and osteoporosis risk allele scores were determined with generalized estimating equations adjusted for body mass index and subject baseline characteristics. The impact of risk allele score on survival was determined by Cox proportional hazards models.
During the study period, 28 subjects (25%) had osteopenia, while 68 subjects (60%) had osteoporosis. Following lung transplantation, BMD by t-score at the lumbar spine increased over time (median 0.09, p=0.0007). BMD was unchanged at the femoral neck (p= 0.4) and hip (p=0.2). The median number of risk alleles was 15 with interquartile range of 13-17. T-scores decreased by 0.012 per year per risk allele (Figure, p=0.009). Risk alleles were not associated with overall survival (HR 1.3, CI 0.9 - 2, adjusted p=0.2).
Osteoporosis was prevalent, but bone mineral density did not decrease for most recipients following transplantation and relatively spared the lumbar spine. However, subjects with increased genetic risk experienced increased loss in bone mineral density. Focused genotyping may be useful for identifying lung transplant candidates at increased risk for osteoporosis and guiding treatment strategies. |
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| ISSN: | 1053-2498 1557-3117 |
| DOI: | 10.1016/j.healun.2020.01.791 |