Biochemical markers of bone turnover in diabetes patients—a meta-analysis, and a methodological study on the effects of glucose on bone markers

Starup-Linde, Jakob; Eriksen, Stine Aistrup; Lykkeboe, Simon; Handberg, Aase; Vestergaard, Peter

doi:10.1007/s00198-014-2676-7

Cited by 195 publications

(127 citation statements)

References 42 publications

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“…However, it is hard to explain how individuals with T2DM can exhibit high porosity [14][15][16][17], since increased cortical porosity reflects increased bone turnover from intracortical surfaces lining the Haversian canals and the endocortical surfaces adjacent to the marrow cavity [18,19]. As T2DM is a condition with low bone turnover [20,21], patients with T2DM would rather be expected to exhibit reduced cortical porosity. In contrast, prior studies reported increased porosity in T2DM patients.…”

Section: Introductionmentioning

confidence: 99%

Women with type 2 diabetes mellitus have lower cortical porosity of the proximal femoral shaft using low-resolution CT than nondiabetic women, and increasing glucose is associated with reduced cortical porosity

Osima

Kral

Borgen

et al. 2017

Bone

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Increased cortical porosity has been suggested as a possible factor increasing fracture propensity in patients with type 2 diabetes mellitus (T2DM). This is a paradox because cortical porosity is generally associated with high bone turnover, while bone turnover is reduced in patients with T2DM. We therefore wanted to test the hypothesis that women with T2DM have lower bone turnover markers (BTM) and lower cortical porosity than those without diabetes, and that higher serum glucose and body mass index (BMI) are associated with lower BTM, and with lower cortical porosity. Increasing glucose and BMI were associated with lower bone turnover suggesting that reduced intracortical and endocortical remodeling leads to reduced porosity and thicker cortices. Using low-resolution clinical CT, cortical porosity was lower in women with T2DM compared to 3 women without diabetes. This indicates that other changes in bone qualities, not increased cortical porosity, are likely to explain the increased fracture propensity in patients with T2DM.

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Section: Introductionmentioning

confidence: 99%

Women with type 2 diabetes mellitus have lower cortical porosity of the proximal femoral shaft using low-resolution CT than nondiabetic women, and increasing glucose is associated with reduced cortical porosity

Osima

Kral

Borgen

et al. 2017

Bone

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“…Bone turnover markers studies in diabetes have had some conflicting results, but the most consistent finding is that markers of resorption (C-terminal cross-linking telopeptide of type I collagen (CTX), N-terminal cross-linking telopeptide of type I collagen (NTX)) and formation (procollagen type I N propeptide (P1NP), osteocalcin) are reduced [47,48]. Methodological studies have excluded a direct effect of glucose in the measurements [48], so the bone turnover markers probably do reflect a true biological effect.…”

Section: Mechanisms Of Action Of T2dm On Bonementioning

confidence: 99%

“…Methodological studies have excluded a direct effect of glucose in the measurements [48], so the bone turnover markers probably do reflect a true biological effect. Histomorphometry in T2D shows decrease in bone volume, osteoid volume, thickness and osteoblast surface, and poor uptake of label indicating reduced bone formation [49,50] consistent with lower turnover from biochemical markers.…”

Section: Mechanisms Of Action Of T2dm On Bonementioning

confidence: 99%

Comparison of Metabolic Risk Factors and Physical Fitness according to Femur Osteoporotic Status in Elderly Women

cho¹,

Lee²,

Kang³

2017

Exerc Sci

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clinicians. However, the limited available evidence suggests that osteoporosis treatment does reduce fracture risk in obesity and T2DM with generally similar efficacy to other patients.Keywords Bone · Obesity · Diabetes · Fat · Fracture Obesity, Type 2 Diabetes and BoneObesity is a major and growing public health problem; for example, in the UK, 40% of adults will be obese by 2025 [1]. Obesity is the most important risk factor for type 2 diabetes (T2DM), and the global prevalence of T2DM is likely to be 592 million by 2035 [2]. As the population ages, the burden of osteoporosis and fragility fracture also increases. Obesity and T2DM have effects on fracture risk, and fractures in T2DM are associated with greater morbidity than in the general population. Understanding how to assess and treat fracture risk in these groups is important for health care planning and individual patients. Additionally, the study of the mechanisms of action of obesity and T2DM on bone has already offered insights that may be applicable in the broader study of osteoporosis, such as the effects of adipokines on bone cells and the effects of collagen glycation on material properties of bone. There are some similarities in the effect of obesity and T2DM on bone, but some important differences such as cortical porosity and collagen glycation.In this review, we describe the effects of obesity and T2DM on fracture risk and discuss possible mechanisms of their effects. We also consider the validity of existing fracture risk prediction tools and efficacy of osteoporosis treatment in these patient groups. AbstractIn an increasingly obese and ageing population, type 2 diabetes (T2DM) and osteoporotic fracture are major public health concerns. Understanding how obesity and type 2 diabetes modulate fracture risk is important to identify and treat people at risk of fracture. Additionally, the study of the mechanisms of action of obesity and T2DM on bone has already offered insights that may be applicable to osteoporosis in the general population. Most available evidence indicates lower risk of proximal femur and vertebral fracture in obese adults. However the risk of some fractures (proximal humerus, femur and ankle) is higher, and a significant number fractures occur in obese people. BMI is positively associated with BMD and the mechanisms of this association in vivo may include increased loading, adipokines such as leptin, and higher aromatase activity. However, some fat depots could have negative effects on bone; cytokines from visceral fat are pro-resorptive and high intramuscular fat content is associated with poorer muscle function, attenuating loading effects and increasing falls risk. T2DM is also associated with higher bone mineral density (BMD), but increased overall and hip fracture risk. There are some similarities between bone in obesity and T2DM, but T2DM seems to have additional harmful effects and emerging evidence suggests that glycation of collagen may be an important factor. Higher BMD but higher fracture risk presents challenges i...

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“…However, moving from the preclinical to the clinical setting has been more difficult in establishing the relationship between this system and metabolic homeostasis. (23,53,54) Bioenergetics of the skeleton More recently, attention has focused on other mechanisms related to stem cell fate; in particular, the metabolic program of MSC progenitors. There is now emerging evidence that adipocytes and osteoblasts have distinct energy utilization pathways as they move down their respective lineages during differentiation.…”

Section: Skeletal Control Of Metabolic Balancementioning

confidence: 99%

“…(21) For example, insulin-resistant obese and T2D patients generally exhibit lower bone turnover than nondiabetic normal subjects, as measured by histomorphometry and serum bone turnover markers. (22)(23)(24) In particular, those with previous vertebral fractures have been shown to have higher sclerostin and lower serum IGF-I and PTH levels consistent with reduced bone formation and lower bone turnover. (25,26) Whether this reflects the insulin-resistant state of the individual and hence impairment in the fast-forward cycle, or another process, remains to be determined.…”

mentioning

confidence: 99%

Energy Excess, Glucose Utilization, and Skeletal Remodeling: New Insights

Lecka‐Czernik

Rosen

2015

Journal of Bone and Mineral Research

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Skeletal complications have recently been recognized as another of the several comorbidities associated with diabetes. Clinical studies suggest that disordered glucose and lipid metabolism have a profound effect on bone. Diabetes-related changes in skeletal homeostasis result in a significant increased risk of fractures, although the pathophysiology may differ from postmenopausal osteoporosis. Efforts to understand the underlying mechanisms of diabetic bone disease have focused on the direct interaction of adipose tissue with skeletal remodeling and the potential influence of glucose utilization and energy uptake on these processes. One aspect that has emerged recently is the major role of the central nervous system in whole-body metabolism, bone turnover, adipose tissue remodeling, and beta cell secretion of insulin. Importantly, the skeleton contributes to the metabolic balance inherent in physiologic states. New animal models have provided the insights necessary to begin to dissect the effects of obesity and insulin resistance on the acquisition and maintenance of bone mass. In this Perspective, we focus on potential mechanisms that underlie the complex interactions between adipose tissue and skeletal turnover by focusing on the clinical evidence and on preclinical studies indicating that glucose intolerance may have a significant impact on the skeleton. In addition, we raise fundamental questions that need to be addressed in future studies to resolve the conundrum associated with glucose intolerance, obesity, and osteoporosis. © 2015 American Society for Bone and Mineral Research. KEY WORDS: BONE-FAT INTERACTIONS; SYSTEMS BIOLOGY; BONE INTERACTORS; CELL/TISSUE SIGNALING; TRANSCRIPTION FACTORS; DISEASES AND DISORDERS OF/RELATED TO BONE Clinical Insight Into the Effect of Disordered Glucose and Lipids Homeostasis on BoneD iabetes mellitus (DM) can be considered a disease of intracellular glucose starvation in muscle and fat, due to either lack of insulin (Type 1 [T1D]) or impaired insulin action (Type 2 [T2D]). Both types of DM are associated with an increase in fractures; however, the skeletal phenotype is very different. T1D patients have reduced bone mineral density (BMD), due to insulin and amylin deficiency, whereas T2D patients have either normal or high BMD. T2D is a disease of disordered energy storage as well as glucose intolerance and altered bone strength. Its prevalence is high and not abating. In the United States, 29.1 million people-9.3% of the population-have diabetes; among them, nearly 60% are characterized as obese (http://www.cdc.gov). Insulin resistance is a characteristic feature of T2D in liver, muscle, and fat, leading to glucose intolerance, elevated cardiometabolic risk factors (eg, low-density lipoprotein [LDL] cholesterol), and excess hepatic glucose output. Visceral adipocytes, in particular, are large and surrounded by fibrous and inflammatory elements.In clinical medicine a major paradox is the relationship of obesity to the skeleton. Obese individuals tend to have higher...

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Biochemical markers of bone turnover in diabetes patients—a meta-analysis, and a methodological study on the effects of glucose on bone markers

Abstract: The dissociative pattern of biochemical bone markers of bone formation and bone resorption present in diabetes patients is thus not caused by glucose per se but may be modulated by unknown factors associated with diabetes mellitus.

Cited by 195 publications

References 42 publications

Women with type 2 diabetes mellitus have lower cortical porosity of the proximal femoral shaft using low-resolution CT than nondiabetic women, and increasing glucose is associated with reduced cortical porosity

Women with type 2 diabetes mellitus have lower cortical porosity of the proximal femoral shaft using low-resolution CT than nondiabetic women, and increasing glucose is associated with reduced cortical porosity

Comparison of Metabolic Risk Factors and Physical Fitness according to Femur Osteoporotic Status in Elderly Women

Energy Excess, Glucose Utilization, and Skeletal Remodeling: New Insights

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