Vertebral Fractures in Individuals With Type 2 Diabetes: More Than Skeletal Complications Alone

OBJECTIVE We aimed to assess whether individuals with type 2 diabetes (T2D) have increased risk of vertebral fractures (VFs) and to estimate nonvertebral fracture and mortality risk among individuals with both prevalent T2D and VFs. RESEARCH DESIGN AND METHODS A systematic PubMed search was performed to identify studies that investigated the relationship between T2D and VFs. Cohorts providing individual participant data (IPD) were also included. Estimates from published summary data and IPD cohorts were pooled in a random-effects meta-analysis. Multivariate Cox regression models were used to estimate nonvertebral fracture and mortality risk among individuals with T2D and VFs. RESULTS Across 15 studies comprising 852,705 men and women, individuals with T2D had lower risk of prevalent (odds ratio [OR] 0.84 [95% CI 0.74–0.95]; I2 = 0.0%; Phet = 0.54) but increased risk of incident VFs (OR 1.35 [95% CI 1.27–1.44]; I2 = 0.6%; Phet = 0.43). In the IPD cohorts (N = 19,820), risk of nonvertebral fractures was higher in those with both T2D and VFs compared with those without T2D or VFs (hazard ratio [HR] 2.42 [95% CI 1.86–3.15]) or with VFs (HR 1.73 [95% CI 1.32–2.27]) or T2D (HR 1.94 [95% CI 1.46–2.59]) alone. Individuals with both T2D and VFs had increased mortality compared with individuals without T2D and VFs (HR 2.11 [95% CI 1.72–2.59]) or with VFs alone (HR 1.84 [95% CI 1.49–2.28]) and borderline increased compared with individuals with T2D alone (HR 1.23 [95% CI 0.99–1.52]). CONCLUSIONS Based on our findings, individuals with T2D should be systematically assessed for presence of VFs, and, as in individuals without T2D, their presence constitutes an indication to start osteoporosis treatment for the prevention of future fractures.

[1]  F. Rivadeneira,et al.  Cohort profile: The OsteoLaus study. , 2019, International journal of epidemiology.

[2]  L. Lix,et al.  Prevalent vertebral fracture on bone density lateral spine (VFA) images in routine clinical practice predict incident fractures. , 2019, Bone.

[3]  M. Levine,et al.  Frailty and Risk of Fractures in Patients With Type 2 Diabetes , 2019, Diabetes Care.

[4]  Jian-ling Du,et al.  Diabetes mellitus and the risk of fractures at specific sites: a meta-analysis , 2019, BMJ Open.

[5]  Varda Shalev,et al.  Epidemiology and correlates of osteoporotic fractures among type 2 diabetic patients , 2018, Archives of Osteoporosis.

[6]  Eric Vittinghoff,et al.  Vertebral Fracture Risk in Diabetic Elderly Men: The MrOS Study , 2018, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[7]  O. Franco,et al.  The Rotterdam Study: 2018 update on objectives, design and main results , 2017, European Journal of Epidemiology.

[8]  M. Frost,et al.  Bone disease in diabetes: another manifestation of microvascular disease? , 2017, The lancet. Diabetes & endocrinology.

[9]  W. Liu,et al.  Risk of low-energy fracture in type 2 diabetes patients: a meta-analysis of observational studies , 2017, Osteoporosis International.

[10]  A. Díez-Pérez,et al.  Excess of all-cause mortality after a fracture in type 2 diabetic patients: a population-based cohort study , 2017, Osteoporosis International.

[11]  C. Cooper,et al.  UK clinical guideline for the prevention and treatment of osteoporosis , 2017, Archives of Osteoporosis.

[12]  M. Amraei,et al.  Fracture risk in patients with type 2 diabetes mellitus and possible risk factors: a systematic review and meta-analysis , 2017, Therapeutics and clinical risk management.

[13]  P. Vestergaard,et al.  MECHANISMS IN ENDOCRINOLOGY: Diabetes mellitus, a state of low bone turnover - a systematic review and meta-analysis. , 2017, European journal of endocrinology.

[14]  S. Volpato,et al.  Muscle dysfunction in type 2 diabetes: a major threat to patient’s mobility and independence , 2016, Acta Diabetologica.

[15]  Xiaozhong Yu,et al.  Comment on Wang et al.: Increased risk of vertebral fracture in patients with diabetes: a meta-analysis of cohort studies , 2016, International Orthopaedics.

[16]  M. Michalak,et al.  Type 2 diabetes and risk of low-energy fractures in postmenopausal women: meta-analysis of observational studies , 2016, Aging Clinical and Experimental Research.

[17]  Yangang Wang,et al.  Increased risk of vertebral fracture in patients with diabetes: a meta-analysis of cohort studies , 2016, International Orthopaedics.

[18]  W. Rathmann,et al.  Fracture risk in patients with newly diagnosed type 2 diabetes: a retrospective database analysis in primary care. , 2015, Journal of diabetes and its complications.

[19]  H. Choi,et al.  Trabecular bone score as an indicator for skeletal deterioration in diabetes. , 2015, The Journal of clinical endocrinology and metabolism.

[20]  Gabriëlle H S Buitendijk,et al.  High Bone Mineral Density and Fracture Risk in Type 2 Diabetes as Skeletal Complications of Inadequate Glucose Control , 2013, Diabetes Care.

[21]  W. Leslie,et al.  TBS (trabecular bone score) and diabetes-related fracture risk. , 2013, The Journal of clinical endocrinology and metabolism.

[22]  Lili Ma,et al.  Association between bone mineral density and type 2 diabetes mellitus: a meta-analysis of observational studies , 2012, European Journal of Epidemiology.

[23]  J. Kanis,et al.  FRAX underestimates fracture risk in patients with diabetes , 2012, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[24]  Eva Negri,et al.  Risk Factors for Falls in Community-dwelling Older People: A Systematic Review and Meta-analysis , 2010, Epidemiology.

[25]  T. Sugimoto,et al.  Diabetic Patients Have an Increased Risk of Vertebral Fractures Independent of BMD or Diabetic Complications , 2009, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[26]  X. Nogués,et al.  Bone mineral density and risk of fractures in aging, obese post-menopausal women with type 2 diabetes. The GIUMO Study , 2009, Aging clinical and experimental research.

[27]  T. Therneau,et al.  Fracture Risk in Type 2 Diabetes: Update of a Population‐Based Study , 2008, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[28]  Laurent Pothuaud,et al.  Correlations between grey-level variations in 2D projection images (TBS) and 3D microarchitecture: applications in the study of human trabecular bone microarchitecture. , 2008, Bone.

[29]  C. Cooper,et al.  European guidance for the diagnosis and management of osteoporosis in postmenopausal women , 2008, Osteoporosis International.

[30]  John Brazier,et al.  Clodronate Reduces the Incidence of Fractures in Community‐Dwelling Elderly Women Unselected for Osteoporosis: Results of a Double‐Blind, Placebo‐Controlled Randomized Study , 2006, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[31]  Karen C Johnson,et al.  Risk of fracture in women with type 2 diabetes: the Women's Health Initiative Observational Study. , 2006, The Journal of clinical endocrinology and metabolism.

[32]  Michael Brownlee,et al.  The pathobiology of diabetic complications: a unifying mechanism. , 2005, Diabetes.

[33]  H. Genant,et al.  Underdiagnosis of Vertebral Fractures Is a Worldwide Problem: The IMPACT Study , 2004, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[34]  S. Wild,et al.  Global prevalence of diabetes: estimates for the year 2000 and projections for 2030. , 2004, Diabetes care.

[35]  Pamela J Schreiner,et al.  Older women with diabetes have a higher risk of falls: a prospective study. , 2002, Diabetes care.

[36]  C. Cooper,et al.  Incidence of clinically diagnosed vertebral fractures: A population‐based study in rochester, minnesota, 1985‐1989 , 1992, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[37]  Harry K. Genant,et al.  Appendicular Bone Density and Age Predict Hip Fracture in Women , 1990 .

[38]  S. Khosla,et al.  Determinants of bone strength and quality in diabetes mellitus in humans. , 2016, Bone.

[39]  Y. Lang,et al.  Diabetes mellitus and risk of hip fractures: a meta-analysis , 2015, Osteoporosis International.

[40]  D. Moher,et al.  Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. , 2010, International journal of surgery.

[41]  O. Johnell,et al.  Risk factors for fragility fracture in middle age. A prospective population-based study of 33,000 men and women , 2006, Osteoporosis International.

[42]  H. K. Genant,et al.  Standardization of Bone Mineral Density at Femoral Neck, Trochanter and Ward’s Triangle , 2001, Osteoporosis International.

[43]  Jacques P. Brown,et al.  Research Notes: The Canadian Multicentre Osteoporosis Study (CaMos): Background, Rationale, Methods , 1999, Canadian Journal on Aging / La Revue canadienne du vieillissement.