Abstract
We investigated independent associations between telomere length and risk of fracture and arthroplasty in UK Biobank participants. Leucocyte telomere length (LTL) was measured in baseline samples using a validated PCR method. We used, in men and women separately, Cox proportional hazards models to calculate the hazard ratio for incident fracture (any, osteoporotic) or arthroplasty (hip or knee) over 1,186,410 person-years of follow-up. Covariates included age, white cell count, ethnicity, smoking, alcohol, physical activity and menopause (women). In further analyses we adjusted for either estimated bone mineral density from heel quantitative ultrasound, handgrip strength, gait speed, total fat mass (bioimpedance) or blood biomarkers, all measured at baseline (2006-2010). We studied 59,500 women and 51,895 men, mean(SD) age 56.4(8.0) and 57.0(8.3) years respectively. During follow-up there were 5,619 fractures; 5,285 hip and 4,261 knee arthroplasties. In confounder-adjusted models, longer LTL was associated with reduced risk of incident knee arthroplasty in both men [hazard ratio/SD (95%CI): 0.93 (0.88,0.97)] and women [0.92 (0.88,0.96)] and hip arthroplasty in men [0.91 (0.87,0.95)] but not women [0.98 (0.94,1.01)]. Longer LTL was weakly associated with reduced risk of any incident fracture in women [hazard ratio/SD (95% CI): 0.96 (0.93,1.00)] with less evidence in men [0.98 (0.93,1.02)]. Associations with incident outcomes were not materially altered by adjustment for heel estimated bone mineral density, grip strength, gait speed, fat mass or blood biomarker measures. In this, the largest study to date, longer LTL was associated with lower risk of incident knee or hip arthroplasty, but only weakly associated with lower risk of fracture. The relative risks were low at a population level, but our findings suggest that common factors acting on the myeloid and musculoskeleletal systems might influence later life musculoskeletal outcomes.
| Original language | English |
|---|---|
| Pages (from-to) | 1997-2004 |
| Number of pages | 8 |
| Journal | Journal of Bone and Mineral Research |
| Volume | 37 |
| Issue number | 10 |
| Early online date | 25 Jul 2022 |
| DOIs | |
| Publication status | Published - 1 Oct 2022 |
Bibliographical note
Funding Information:This work was supported by grants from Medical Research Council (MRC) [MC_PC_21003; MC_PC_21001], Bupa Foundation, British Heart Foundation, National Institute for Health and Care Research (NIHR) Southampton Biomedical Research Centre, University of Southampton, and University Hospital Southampton NHS Foundation Trust, NIHR Oxford Biomedical Research Centre, University of Oxford, Wellcome Trust (209233/Z/17/Z) and the UK Royal Osteoporosis Society Osteoporosis and Bone Research Academy. EMC has been supported by the Wellcome Trust (201268/Z/16/Z) and currently by NIHR. This work uses the UK Biobank resource (approved application 6077). PMM acknowledges generous personal and research support from the Edmond J Safra Foundation and Lily Safra, a National Institute for Health Research (NIHR) Senior Investigator Award, the UK Dementia Research Institute, the NIHR Biomedical Research Centre and the British Heart Foundation Centre of Excellence at Imperial College London.
Publisher Copyright:
© 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).