Sclerostin antibody treatment improves bone mass, bone strength, and bone defect regeneration in rats with type 2 diabetes mellitus

Hamann, Christine; Rauner, Martina; Höhna, Y.; Bernhardt, Ricardo; Mettelsiefen, Jan; Goettsch, Claudia; Günther, Klaus‐Peter; Stolina, Marina; Han, Chun-Ya; Asuncion, Frank; Ominsky, Michael S.; Hofbauer, Lorenz C.

doi:10.1002/jbmr.1803

Cited by 113 publications

(111 citation statements)

References 35 publications

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“…To date, however, there are no human data on the effect of intermittent PTH in T1DM patients. Sclerostin antibody has been tested in animal models with T2DM, where it increased bone mass and strength, but not in the setting of T1DM (125). Unfortunately no clinical studies are yet available to confirm this in humans.…”

Section: Fracture Preventionmentioning

confidence: 99%

MECHANISMS IN ENDOCRINOLOGY: Mechanisms and evaluation of bone fragility in type 1 diabetes mellitus

Hough

Pierroz²,

Cooper

et al. 2016

European Journal of Endocrinology

131

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Subjects with type 1 diabetes mellitus (T1DM) have decreased bone mineral density and an up to sixfold increase in fracture risk. Yet bone fragility is not commonly regarded as another unique complication of diabetes. Both animals with experimentally induced insulin deficiency syndromes and patients with T1DM have impaired osteoblastic bone formation, with or without increased bone resorption. Insulin/IGF1 deficiency appears to be a major pathogenetic mechanism involved, along with glucose toxicity, marrow adiposity, inflammation, adipokine and other metabolic alterations that may all play a role on altering bone turnover. In turn, increasing physical activity in children with diabetes as well as good glycaemic control appears to provide some improvement of bone parameters, although robust clinical studies are still lacking. In this context, the role of osteoporosis drugs remains unknown.

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Section: Fracture Preventionmentioning

confidence: 99%

MECHANISMS IN ENDOCRINOLOGY: Mechanisms and evaluation of bone fragility in type 1 diabetes mellitus

Hough

Pierroz²,

Cooper

et al. 2016

European Journal of Endocrinology

131

View full text Add to dashboard Cite

show abstract

“…At later time points, this leads to higher mineral content in the abundantly formed new bone, thereby potentially increasing mechanical stability. Furthermore, early reports that successfully used Sost antibody treatment to promote fracture healing relied heavily on models that primarily healed by intramembranous bone formation [94,140,152,153]. This suggested that SostAb may be beneficial in problematic fracture healing that results from poor osteogenesis; however, Li et al (2011) [154] reported fracture repair in an endochondral model in Sost -/-mice, and Feng et al (2015) [155] reported similar results with Sost antibody treatment, suggesting that fracture repair may benefit from early intervention by reducing sclerostin levels, rather than only during osteogenesis.…”

Section: Discussionmentioning

confidence: 99%

“…In another study, murine Sost antibodies increase bone mineral density (BMD) in ovariectomized rats, and decrease fracture risk [93], revealing that SOST antibody may also be beneficial for those with osteoporosis. Sost antibody treatment on T2DM rats with a low bone mass phenotype has also revealed increased bone formation, however this effect has not been examined in T1DM mice [94]. Sost antibody have also shown an anabolic effect in fracture healing with enhanced bone formation and is mechanically stable [95].…”

Section: Sost As a Wnt Antagonist And Sost Antibodymentioning

confidence: 99%

“…Type 2 diabetic patients have elevated circulating SOST levels compared to nondiabetic patients [138], suggesting that Wnt signaling is altered in diabetic patients and may contribute to the observed osteopenia and delayed healing phenotype. Sost antibodies (SostAb) have been shown to enhance bone healing in ovariectomized rats [139,140] by increasing bone formation and mass due to enhanced osteoblast function as determined by elevated levels of osteocalcin, a marker of osteoblast activity SostAb treatment in type 2 diabetic rats has also been shown to improve bone mass and strength [94].…”

Section: Introductionmentioning

confidence: 99%

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Determining the Role of Sost and Sostdc1 During Fracture Healing

Yee¹

2016

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“…In post hoc analysis of the FIT alendronate and HORIZON zoledronic acid trial, fracture reduction was similar in participants with and without diabetes [69]. Teriparatide and sclerostin antibodies increase BMD in Zucker diabetic rats, but the rats' bone phenotype is different from human T2DM, and there is not yet available information on these drugs in humans with T2DM [70,71].…”

Section: Fracture Risk Assessment and Osteoporosis Treatment In T2dmmentioning

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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Sclerostin antibody treatment improves bone mass, bone strength, and bone defect regeneration in rats with type 2 diabetes mellitus

Cited by 113 publications

References 35 publications

MECHANISMS IN ENDOCRINOLOGY: Mechanisms and evaluation of bone fragility in type 1 diabetes mellitus

MECHANISMS IN ENDOCRINOLOGY: Mechanisms and evaluation of bone fragility in type 1 diabetes mellitus

Determining the Role of Sost and Sostdc1 During Fracture Healing

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

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