Increased bone density and decreased bone turnover, but no evident alteration of fracture susceptibility in elderly women with diabetes mellitus

Gerdhem, Paul; Isaksson, Anders; Åkesson, Kristina; Obrant, Karl

doi:10.1007/s00198-005-1877-5

Cited by 179 publications

(135 citation statements)

References 32 publications

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“…Change in bone turnover markers varied considerably between individual studies. While HIV, anti-retroviral treatment, diabetes, glycaemic control and the postmenopausal state are all known to influence concentrations of turnover markers [41][42][43], no consistent changes in these markers were observed within the different study populations incorporated in this meta-analysis. Our findings corroborate the results of animal studies, which have also reported inconsistent effects of TZDs on bone turnover [11].…”

Section: Discussionmentioning

confidence: 72%

The effect of thiazolidinediones on bone mineral density and bone turnover: systematic review and meta-analysis

2015

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Aims/hypothesis Thiazolidinediones (TZDs) are associated with an increased risk of fracture but the mechanism is unclear. We sought to determine the effect of TZDs on bone mineral density (BMD) and bone turnover markers. Methods PubMed, EMBASE and Cochrane CENTRAL databases were searched from inception until January 2015 for randomised controlled trials comparing TZDs with metformin, sulfonylureas or placebo, and those reporting changes in BMD and/or bone turnover markers. The primary outcome was percentage change in BMD from baseline and results were pooled with random effects meta-analyses. Results In all, 18 trials were included in the primary analyses and another two were included in the sensitivity analyses (n=3,743, 50% women, mean age 56 years, median trial duration 48 weeks). TZDs decreased BMD at the lumbar spine (difference −1.1% [95% CI −1.6, −0.7]; p<0.0001), total hip (−1.0% [−1.4, −0.6]; p<0.0001) and forearm (−0.9% [−1.6, −0.3]; p=0.007). There were statistically non-significant decreases in BMD at the femoral neck (−0.7% [−1.4, 0.0]; p=0.06) and total body (−0.3% [−0.5, 0.0]; p=0.08). Five trials (n=450) showed no statistically significant difference in percentage change in BMD between the TZD group and controls up to 1 year following TZD withdrawal. In 14 trials, the effect of TZD treatment on turnover markers varied considerably between individual studies. Conclusions/interpretation Treatment with TZDs results in modest bone loss that may not be reversed 1 year after cessation of treatment.

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Section: Discussionmentioning

confidence: 72%

The effect of thiazolidinediones on bone mineral density and bone turnover: systematic review and meta-analysis

2015

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“…Moreover, we found FPG was independently correlated with osteocalcin in men, and HbA1c was independently correlated with osteocalcin in both premenopausal and postmenopausal women. Studies in vivo or in vitro have demonstrated that in hyperglycemic states, the osteoblast mass and possibly function are decreased, which suppresses osteocalcin synthesis and secretion (18,19), resulting in impaired bone turnover and reduced bone formation (20). Conversely, osteocalcin also has an impact on glucose regulation.…”

Section: Discussionmentioning

confidence: 99%

Serum osteocalcin concentrations in relation to glucose and lipid metabolism in Chinese individuals

Zhou¹,

Ma²,

Li³

et al. 2009

European Journal of Endocrinology

176

128

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Objectives: Osteocalcin, a bone-derived protein, has recently been reported to affect energy metabolism. We investigated the relationship between serum osteocalcin and parameters of adiposity, glucose tolerance, and lipid profile in Chinese subjects. Methods: Serum osteocalcin was measured by electrochemiluminescence immunoassay in 254 men (128 with newly diagnosed type 2 diabetes mellitus (T2DM) and 126 with normal glucose tolerance (NGT)), 66 premenopausal women (33 with T2DM and 33 with NGT) as well as 180 postmenopausal women (92 with T2DM and 88 with NGT). Their associations with parameters of adiposity, glucose tolerance, and lipid profile were examined. Results: Serum osteocalcin concentrations in diabetic patients were significantly lower than those in NGT subjects after adjusted for age, gender, and body mass index (PZ0.003). Postmenopausal women had higher osteocalcin concentrations than premenopausal women and men (both P!0.001). Multiple stepwise regression analysis showed that age, %fat, high-density lipoprotein cholesterol, fasting plasma glucose, and fasting serum insulin were independently associated with osteocalcin in men (P!0.05). Age and HbA1c were independently correlated with osteocalcin in postmenopausal women. Besides age and HbA1c, serum triglyceride was also an independent factor influencing osteocalcin in premenopausal women. In addition, osteocalcin was also positively associated with homeostasis model assessment of b-cell function. Furthermore, multiple logistic regression analysis demonstrated that osteocalcin was independently associated with T2DM. Conclusions: Serum osteocalcin was closely associated with not only fat and glucose metabolism but also with lipid metabolism.

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“…Thus, osteocalcin was inversely associated with plasma glucose, insulin levels, and serum triglycerides in elderly men and women as well as elderly men with high cardiovascular risk (183,184,185,186,187,188). Also, osteocalcin was lower in patients with T2DM (189,190,191) and gestational diabetes (192). Moreover, in active acromegaly, a condition with profound insulin resistance, osteocalcin levels were the major determinant of insulin resistance and b-cell function, both in vivo and in vitro (193).…”

Section: Metabolic Aspects In Relation To a Homeostatic Model Involvimentioning

confidence: 99%

Genetics in Endocrinology: Autosomal dominant osteopetrosis revisited: lessons from recent studies

Bollerslev

Henriksen

Nielsen

et al. 2013

European Journal of Endocrinology

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Systematic studies of autosomal dominant osteopetrosis (ADO) were followed by the identification of underlying mutations giving unique possibilities to perform translational studies. What was previously designated ADO1 turned out to be a high bone mass phenotype caused by a missense mutation in the first propeller of LRP5, a region of importance for binding inhibitory proteins. Thereby, ADO1 cannot be regarded as a classical form of osteopetrosis but must now be considered a disease of LRP5 activation. ADO (Albers-Schönberg disease, or previously ADO2) is characterized by increased number of osteoclasts and a defect in the chloride transport system (ClC-7) of importance for acidification of the resorption lacuna (a form of Chloride Channel 7 Deficiency Osteopetrosis). Ex vivo studies of osteoclasts from ADO have shown that cells do form normally but have reduced resorption capacity and an expanded life span. Bone formation seems normal despite decreased osteoclast function. Uncoupling of formation from resorption makes ADO of interest for new strategies for treatment of osteoporosis. Recent studies have integrated bone metabolism in whole-body energy homeostasis. Patients with ADO may have decreased insulin levels indicating importance beyond bone metabolism. There seems to be a paradigm shift in the treatment of osteoporosis. Targeting ClC-7 might introduce a new principle of dual action. Drugs affecting ClC-7 could be antiresorptive, still allowing ongoing bone formation. Inversely, drugs affecting the inhibitory site of LRP5 might stimulate bone formation and inhibit resorption. Thereby, these studies have highlighted several intriguing treatment possibilities, employing novel modes of action, which could provide benefits to the treatment of osteoporosis.

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Increased bone density and decreased bone turnover, but no evident alteration of fracture susceptibility in elderly women with diabetes mellitus

Cited by 179 publications

References 32 publications

The effect of thiazolidinediones on bone mineral density and bone turnover: systematic review and meta-analysis

The effect of thiazolidinediones on bone mineral density and bone turnover: systematic review and meta-analysis

Serum osteocalcin concentrations in relation to glucose and lipid metabolism in Chinese individuals

Genetics in Endocrinology: Autosomal dominant osteopetrosis revisited: lessons from recent studies

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