The pathogenesis for low-trauma wrist fractures in men is not fully understood. This study found that these men had evidence of significantly higher bone turnover compared with control subjects. Bone turnover markers were negative predictors of bone mineral density and were a predictor of fracture.
Men with distal forearm fractures have reduced bone density, an increased risk of osteoporosis and of further fractures. The aim of this study was to investigate whether or not men with distal forearm fractures had evidence of altered bone turnover activity.
Fifty eight men with low-trauma distal forearm fracture and 58 age-matched healthy control subjects were recruited. All subjects underwent a DXA scan of the forearm, both hips, and lumbar spine, biochemical investigations, and health questionnaires. Measurements of beta crosslaps (βCTX), procollagen type I N-terminal propeptide (PINP), sclerostin, Dickkopf-1 (Dkk1), and fibroblast growth factor 23 (FGF 23) were made.
Men with fracture had significantly higher PINP than controls at 39.2 ng/ml (SD 19.5) versus 33.4 ng/ml (SD13.1) (p<0.001). They also had significantly higher βCTX at 0.45 ng/ml (SD 0.21) versus 0.37 ng/ml (SD 0.17) (p= 0.037). Fracture subjects had significantly lower aBMD and PINP was a negative predictor of aBMD at the total hip and βCTX a negative predictor of forearm aBMD. Sclerostin was a positive predictor of aBMD at the lumbar spine and hip sites. Sex hormone binding globulin (SHBG) at 37nmol/L (SD 15.0) was lower in fracture cohort compared to 47.9 nmol/L (SD 19.2) (p=0.001) in control. Multiple regression revealed that the best model for prediction of fracture included SHBG, P1NP, and ultra-distal forearm aBMD. The likelihood of distal forearm fracture was decreased by 5.1% for each nmol/L increase in SHBH and by 1.4% for every mg/cm2 increase in ultra-distal forearm aBMD, but increased by 6.1 % for every ng/ml increase in P1NP. Men in the highest quartile of PINP had a significantly greater likelihood of distal forearm fracture than those in the lowest quartile.
The fracture group had significantly higher PINP and βCTX compared with the control group, and these markers were negative predictors of aBMD at the total hip and forearm sites, respectively. Sclerostin was a positive predictor of the variance of spinal and hip aBMD. Likelihood of forearm fracture was best predicted by a combination of SHBG, PINP, and ultra-distal forearm aBMD. Findings of such cross-sectional data should be treated with caution, as longitudinal studies would be required to confirm or refute them.
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Tuck SP, Francis RM, Hanusch B (2012) Osteoporosis in men. Oxford Rheumatology Library: Osteoporosis- edited by Gavin Clunie and Richard Keen. Oxford University Press
Tuck SP, Raj N, Summers GD (2002) Is distal forearm fracture in men due to osteoporosis? Osteoporos Int 13(8):630–636
Hanusch BC, Tuck SP, McNally RJQ et al (2017) Does regional loss of bone mineral density explain low trauma distal forearm fractures in men (the MrF study)? Osteoporos Int 28(10):2877–2886
Vasikaran S, Eastell R, Bruyere O et al (2011) Markers of bone turnover for the prediction of fracture risk and monitoring of osteoporosis treatment: a need for international standards. Osteoporos Int 22(2):391–420
Atkins GJ, Findlay DM (2012) Osteocyte regulation of bone mineral: a little give and take. Osteoporos Int 23(8):2067–2079
Datta HK, Ng WF, Walker JA, Tuck SP, Varanassi SS (2008) Cell biology of bone. J Clin Pathol 61(5):577–587
Hay E, Bouaziz W, Funck-Brentano T, Cohen-Solal M (2016) Sclerostin and bone aging: a mini review. Gerentology 62:618–623
Abdallah E, Mosbath O, Khalifa G, Metwaly A, El-Bendary O (2016) Assessment of the relationship between serum soluble Klotho and carotid intima-media thickness and left ventricular dysfunction in hemodialysis patients. Kidney Res Clin Pract 35(1):42–49
Heiland GR, Appel H, Poddabnyy D et al (2012) High level of functional dickkopf-1 predicts protection from syndesmophyte formation in patients with ankylosing spondylitis. Ann Rheum Dis 71(4):572–574
Stoch SA, Zajic S, Stone JA, Miller DL, van Bortel L, Lasseter KC, Pramanik B, Cilissen C, Liu Q, Liu L, Scott BB, Panebianco D, Ding Y, Gottesdiener K, Wagner JA (2013) Odanacatib, a selective cathepsin K inhibitor to treat osteoporosis: safety, tolerability, pharmacokinetics and pharmacodynamics--results from single oral dose studies in healthy volunteers. Br J Clin Pharmacol 75(5):1240–1254
Lapauw B, Vandewalle S, Taes Y eta l. (2013) Serum sclerostin levels in men with idiopathic osteoporosis. Eur J Endocrinol 168:615–620
Pernu P, Gaddnas F, Risteli J et al (2015) Type 1 and 3 collagen production by bone marrow mesenchymal stromal cells is suppressed in vitro after exposure to sepsis patient serum. Intens Care Med Exp 3:A639
Szulc P, Munoz F, Claustrat B, Gannero P, Marcland F, Duboeaf F, Delmas PD (2001) Bioavailable estradiol may be an important determinant of osteoporosis in men: the MINOS study. J Clin Endocrinol Metab 86(1):192–199
Evans SF, Davie MW (2002) Low body size and elevated SHBG distinguish men with idiopathic vertebral fracture. Calcif Tissue Int 70:9–15
Pietschmann P, Kudlacek S, Grisar J, Spitzauer S, Woloszczuk W, Willvonseder R, Peterlik M (2001) Bone turnover markers and sex hormones in men with idiopathic osteoporosis. Euro J Clin Inv 31(5):444–451
Tuck SP, Scane AC, Francis RM et al (2008) A case control study of sex steroids and bone turnover in men with symptomatic vertebral fractures. Bone 43(6):999–1005
Montoya MJ, Giner M, Miranda C, Vázquez MA, Caeiro JR, Guede D, Pérez-Cano R (2014) Microstructural trabecular bone from patients with osteoporotic hip fracture or osteoarthritis: its relationship with bone mineral density and bone remodelling markers. Maturitas 79(3):299–305
Chubb SA, Byrnes E, Manning C et al (2015) Reference intervals for bone turnover markers and their association with incident hip fractures in older men: the health in men study. J Clin Endocrinol Metab 100(1):90–99
Yoshimura N, Muraki S, Oka H, Kawaguchi H, Nakamura K, Akune T (2011) Biochemical markers of bone turnover as predictors of osteoporosis and osteoporotic fractures in men and women: a 10 years follow up of the Taiji cohort. Mod Rheumatol 21(6):608–620
Ardawi MS, Rouzi AA, Al-Sibiani SA et al (2012) High serum sclerostin predicts the occurrence of osteoporotic fractures in postmenopausal women: the Center of Excellence for Osteoporosis Research Study. J Bone Miner Res 27(12):2592–2602
Polyzos SA, Anatasilakis AD, Bratengeier C et al (2012) Serum sclerostin levels positively correlate with lumbar spinal bone mineral density in postmenopausal women--the six-month effect of risedronate and teriparatide. Osteoporos Int 23(3):1171–1176
Garnero P, Sornay-Rendu E, Munoz F, Borel O, Chapurlat RD (2013) Association of serum sclerostin with bone mineral density, bone turnover, steroid and parathyroid hormones, and fracture risk in postmenopausal women: the OFELY study. Osteoporos Int 24(2):489–494
Reppe S, Noer A, Grimholt RM, Halldórsson BV, Medina-Gomez C, Gautvik VT, Olstad OK, Berg JP, Datta H, Estrada K, Hofman A, Uitterlinden AG, Rivadeneira F, Lyle R, Collas P, Gautvik KM (2015) Methylation of bone sclerostin, its mRNA, and serum sclerostin levels correlate strongly with fracture risk in postmenopausal women. J Bone Miner Res 30(2):249–256
Gaudio A, Pennizi P, Bratengeier C et al (2010) Increased sclerostin serum levels associated with bone formation and resorption markers in patients with immobilization-induced bone loss. J Clin Endocrinol Metab 95(5):2248–2253
Kalogeroulos M, Varanasi SS, Olstad OK et al (2010) Zic1 transcription factor in bone: neural developmental protein regulates mechanotransduction in osteocytes. FASEB J 24(8):2893–2903
Mirza MA, Karlsson MK, Mellstrom D et al (2011) Serum fibroblast growth factor-23 (FGF-23) and fracture risk in elderly men. J Bone Miner Res 26:4857–4864
Lane NE, Parini N, Corr M et al (2013) Association of serum fibroblast growth factor 23 (FGF23) and incident fractures in older men: the Osteoporotic fractures in men (Mr Os) study. J Bone Miner Res 28(11):2325–2332
Lourneau C, Soudan B, d’Herbomez M eta l. (2004) Sex hormone binding globulin, estradiol and bone turnover markers in male osteoporosis. Bone 34(6):933–939
Legrand E, Hedde C, Gallois Y et al (2001) Osteoporosis in men: a potential role for the sex hormone binding globulin. Bone 29(1):90–95
Risto O, Hammer E, Hammer K et al (2012) Elderly men with a history of distal radius fracture have significantly lower calcaneal bone density and free androgen index than age-matched controls. Aging Male 1591:59–62
Rucker D, Ezzat S, Diamandi A, Khosravi J, Hanley DA (2004) IGF-1 and testosterone levels are predictors of bone mineral density in healthy community dwelling men. Clin Endocrinol 60(45):491–499
Slemenda CW, Longcope C, Zhou L, Hui SL, Peacock M, Johnston CC (1997) Sex steroids and bone mass in older men. Positive associations with serum estrogens and negative associations with androgens. J Clin Invest 100(7):1755–1759
Martinez Diaz-Guerra G, Hawkins F, Rapado A et al (2001) Hormonal and anthropometric predictors of bone mass in healthy elderly men: major effect of sex hormone binding globulin, parathyroid hormone and body weight. Osteoporos Int 12(3):178–184
Center JR, Nguyen TV, Sambrood PN, Eisman JA (2000) Hormonal and biochemical parameters and osteoporotic fractures in elderly men. J Bone Miner Res 15(7):1405–1411
Bjornerem A, Emaus N, Berntsen GK et al (2007) circulating sex steroids, sex hormone binding globulin and longitudinal changes in forearm bone density in postmenopausal women and men: the Tromso study. Calcif Tissue Int 81(2):65–72
Cawthorn PM, Schousboe JT, Harrison SL et al (2016) Sex hormones, sex hormone binding globulin and vertebral fractures in older men. Bone 84:271–278
Vandenput L, Mellstrom D, Kindmark A et al (2016) High serum SHBG predicts incident vertebral fractures in elderly men. J Bone Miner Res 31(3):683–689
El Maghraoui A, Ouzzif Z, Mounach A et al (2011) The relationship between sex steroids, bone turnover and vertebral fracture prevalence in asymptomatic men. Bone 49(4):853–857
Mellstrom D, Vandenput L, Mallmin H et al (2008) Older men with low serum estradiol and high SHBG have an increased risk of fractures. J Bone Miner Res 23(10):1552–1560
Wolfl C, Englert S, Moghaddam AA et al (2013) Time course of 25(OH) D3 vitamin D3 as well as PTH (parathyroid hormone) during fracture healing of patients with normal and low bone mineral density (BMD). BMC Musculoskelatal Diod 14:6. https://doi.org/10.1186/1471-2474-14.6
Ingle BM, Hay SM, Bottjer HM, Eastell R (1999) Changes in bone mass and bone turnover following distal forearm fracture. Osteoporos Int 10:399–407
Hojsager FD, Rand MS, Pederson SB, Nissen N, Jorgensen NR (2019) Fracture-induced changes in biomarkers CTX, PINP, OC and BAP- a systematic review. Osteoporos Int 30:2381–2389
The authors would like to thank all patients and volunteers who took part in the study. They are grateful to Mrs. Gill Wheater for undertaking the laboratory tests and Mrs. Jackie Bates for performing the DXA scans.
This study was funded by a grant from the National Osteoporosis Society (Grant number: 75/190).
Statement of Human Rights
The study has been approved by the National Research Ethics Committee North East, UK (REC reference 10/H0908/15) and has been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.
Conflicts of interest
Birgit Hanusch, Stephen Tuck and Harish Datta have received grants from the National Osteoporosis Society. Birgit Hanusch, Stephen Tuck, Harish Datta, and Julie Walker are also supported by an innovative award from the National Osteoporosis Society (Grant number CS/250). Stephen Tuck has received speaker fees from Ely Lilly, Servier, Internist, and Amgen. Richard McNally and Michael Prediger declare that they have no conflicts of interest.
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Hanusch, B., Prediger, M., Tuck, S. et al. Bone turnover markers as determinants of bone density and fracture in men with distal forearm fractures: the pathogenesis examined in the Mr F study. Osteoporos Int (2021). https://doi.org/10.1007/s00198-021-06001-6
- Bone turnover markers
- Forearm fracture