Disentangling the association between diabetes and bone disease
2017; Elsevier BV; Volume: 5; Issue: 10 Linguagem: Inglês
10.1016/s2213-8587(17)30289-9
ISSN2213-8595
AutoresKatrine Hygum, Bente Langdahl, Jakob Starup‐Linde,
Tópico(s)Bone Metabolism and Diseases
ResumoWe welcome the timely Personal View on bone disease in diabetes by Vikram Shanbhogue and colleagues.1Shanbhogue VV Hansen S Frost M Brixen K Hermann AP Bone disease in diabetes: another manifestation of microvascular disease?.Lancet Diabetes Endocrinol. 2017; 5: 827-838Summary Full Text Full Text PDF PubMed Scopus (71) Google Scholar We believe that the increased fracture risk in patients with diabetes is caused by multiple factors including insulin deficiency, hyperinsulinaemia, an altered incretin response, obesity, use of glucose-lowering drugs, use of antihypertensive and lipid-lowering drugs, comorbidities, falls, and diabetes complications. We suggest that interplay of these factors causes the increased fracture risk in patients with diabetes and that diabetic bone disease is not predominantly attributable to the presence of microvascular disease. If microvascular disease has a major role in the increased fracture risk in diabetes, we would expect consistent reporting of this association in large registry studies. However, in a Danish population-based study2Vestergaard P Rejnmark L Mosekilde L Diabetes and its complications and their relationship with risk of fractures in type 1 and 2 diabetes.Calcif Tissue Int. 2009; 84: 45-55Crossref PubMed Scopus (202) Google Scholar with data from more than 14 000 patients with diabetes, an increased risk of fracture was reported in patients with type 1 and type 2 diabetes without microvascular complications compared with controls, when adjusted for comorbidities, pharmaceutical use, and socioeconomic factors, whereas neither presence of neuropathy nor retinopathy increased the fracture risk. Although microvascular disease has been associated with alterations in bone microarchitecture evaluated by high-resolution peripheral quantitative CT (HRpQCT),1Shanbhogue VV Hansen S Frost M Brixen K Hermann AP Bone disease in diabetes: another manifestation of microvascular disease?.Lancet Diabetes Endocrinol. 2017; 5: 827-838Summary Full Text Full Text PDF PubMed Scopus (71) Google Scholar the relation between changes in bone microarchitecture and fracture risk is still not unravelled. In our study of 51 patients with type 1 diabetes and 66 patients with type 2 diabetes,3Starup-Linde J Lykkeboe S Gregersen S et al.Bone structure and predictors of fracture in type 1 and type 2 diabetes.J Clin Endocrinol Metab. 2016; 101: 928-936Crossref PubMed Scopus (58) Google Scholar we identified no effect of the presence of microvascular disease on cortical nor trabecular microarchitecture, as measured by HRpQCT. Hence, our data suggest that microvascular disease does not affect bone microarchitecture. Diabetes is characterised as a state of low bone turnover, as determined by concentrations of circulating bone turnover markers;4Hygum K Starup-Linde J Harslof T Vestergaard P Langdahl BL Diabetes mellitus, a state of low bone turnover—a systematic review and meta-analysis.Eur J Endocrinol. 2017; 176: R137-R157Crossref PubMed Scopus (182) Google Scholar however, a wide range of bone turnover markers were all unaffected by microvascular disease in a recent study5Starup-Linde J Lykkeboe S Gregersen S et al.Differences in biochemical bone markers by diabetes type and the impact of glucose.Bone. 2016; 83: 149-155Summary Full Text Full Text PDF PubMed Scopus (49) Google Scholar of 98 patients with type 1 diabetes and 96 patients with type 2 diabetes. In the same study,5Starup-Linde J Lykkeboe S Gregersen S et al.Differences in biochemical bone markers by diabetes type and the impact of glucose.Bone. 2016; 83: 149-155Summary Full Text Full Text PDF PubMed Scopus (49) Google Scholar microvascular complications were only associated with an increase in concentrations of the bone resorption marker C-telopeptide of type 1 collagen. The mechanisms of diabetic bone disease are still not fully revealed. Microvascular disease might contribute to the increased fracture risk in patients with diabetes. However, based on the existing evidence, the accepted characteristics of diabetic bone disease as a state of low bone turnover needs further study. In view of the increasing number of patients with diabetes and thus an increasing population-attributable risk of fracture, it is important to uncover predictors of fracture as well as treatment approaches for diabetic bone disease. BLL reports personal fees from Amgen, Eli Lilly, UCB, and Teva, and grants from Amgen and Novo Nordisk. KH and JS-L declare no competing interests. Bone disease in diabetes: another manifestation of microvascular disease?Type 1 and type 2 diabetes are generally accepted to be associated with increased bone fracture risk. However, the pathophysiological mechanisms of diabetic bone disease are poorly understood, and whether the associated increased skeletal fragility is a comorbidity or a complication of diabetes remains under debate. Although there is some indication of a direct deleterious effect of microangiopathy on bone, the evidence is open to question, and whether diabetic osteopathy can be classified as a chronic, microvascular complication of diabetes remains uncertain. Full-Text PDF Disentangling the association between diabetes and bone disease – Authors' replyWe appreciate the interest in our Personal View and thank Katrine Hygum and colleagues for their comments. We also recognise the complexity and multifactorial nature of diabetic bone disease, but still find strong indications for the key role of microvascular disease in diabetic bone disease. Although the results of the Danish register-based study1 with data from more than 14 000 patients with diabetes suggested that neither diabetic eye disease nor neuropathy added to the risk of fractures, presence of diabetic kidney disease doubled the risk of fracture in comparison with patients with diabetes who had no microvascular disease. Full-Text PDF
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