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Assessment of the genetic and clinical determinants of fracture risk: genome wide association and mendelian randomisation study

BMJ 2018; 362 doi: https://doi.org/10.1136/bmj.k3225 (Published 29 August 2018) Cite this as: BMJ 2018;362:k3225

Re: Assessment of the genetic and clinical determinants of fracture risk: genome wide association and mendelian randomisation study

To the Editor
The research article by Trajanoske et al [1] provided evidence against a causal effect of several proposed clinical risk factors for fracture (e.g., diabetes, rheumatoid arthritis, and vitamin D). The authors examined fourteen clinical risk factors. However, no assessment was made to examine chronic renal failure and dialysis as clinical risk factors of fractures [2]. Falls and fractures are common in these patients particularly elderly and dialysis patients, possibly because of muscle weakness, friability, and deterioration of cognition [3]. The pathogenesis of bone disease in these patients is complex and cannot be related to one simple risk factor identified in the study. These changes may include disturbance in systemic mineral metabolism, collapse of physiological feedback mechanisms, parathyroid hormone changes, cortical bone changes, changes in alkaline phosphatase, changes in bone dynamics, and several other bone-related metabolic changes [4]. We believe that testing this category of risk factor is missing and should be considered in the study.

References
1. Trajanoska K, Morris JA, Oei L, Zheng HF, Evans DM, Kiel DP, Ohlsson C, Richards JB, Rivadeneira F; GEFOS/GENOMOS consortium and the 23andMe research team. Assessment ofthe genetic and clinical determinants of fracture risk: genome wide association and mendelian randomisation study. BMJ. 2018 Aug 29;362:k3225.
2. Fishbane S, Hazzan AD, Jhaveri KD, Ma L, Lacson E Jr. Bone Parameters and Risk of Hip and Femur Fractures in Patients on Hemodialysis. Clin J Am Soc Nephrol. 2016 Jun 6;11(6):1063-72.
3. Kazama JJ. Chronic kidney disease and fragility fracture. Clin Exp Nephrol. 2017 Mar;21(Suppl 1):46-52.
4. Yamamoto S, Fukagawa M. Uremic Toxicity and Bone in CKD. J Nephrol. 2017 Oct;30(5):623-627.

Competing interests: No competing interests

02 September 2018
Samy A. AZER
Professor of Medical Education and Research
King Saud university, College of Medicine, Saudi Arabia
P O Box 2925, Riyadh 11461, Saudi Arabia