The Role of Vitamin D in the Metabolic Homeostasis of Diabetic Bone

Abstract

Most studies across a variety of geographic locations suggest that vitamin D insufficiency is more common in individuals with type 1 diabetes (T1D) compared to the general population. In type 2 diabetes (T2D), while obesity is commonplace and lower vitamin D levels are present in obese adolescents and adults, the association between vitamin D insufficiency and T2D is less clear. Studies suggest that the relationship between T2D and vitamin D may be concurrently influenced by ethnicity, geography, BMI and age. None-the-less, diabetic osteopathy is a significant co-morbidity of both forms of diabetes, and is characterized by micro-architectural changes that decrease bone quality leading to an increased risk for bone fracture in both disorders. The question remains, however, to what degree vitamin D homeostasis contributes to or exacerbates skeletal pathology in diabetes. Proposed mechanisms for vitamin D deficiency in diabetes include: 1) genetic predisposition (T1D); 2) increased BMI (T2D); 3) concurrent albuminuria (T1D or T2D); or 4) exaggerated renal excretion of vitamin D metabolites or vitamin D binding protein (T1D, T2D, animal models). The specific effects of vitamin D treatment on diabetic osteoporosis have been examined in rodents, and demonstrate skeletal improvements even in the face of untreated diabetes. However, human clinical trial data examining whether vitamin D status can be directly related to or is predictive of bone quality and fracture risk in those with diabetes is still needed. Herein, we provide a review of the literature linking vitamin D, diabetes and skeletal health.

Skeletal Status, Body Composition, and Glycaemic Control in Adolescents with Type 1 Diabetes Mellitus

“…Our results demonstrate that a physiologically relevant well-controlled T1DM in young patients can improve the development of bone mass and that long-term HbA1c < 8% levels are beneficial to bones. Moreover, the effects of vitamin D deficiency on skeletal muscle functioning usually also accompany diabetes, and may be an important factor responsible for decreased muscle mass [ 76 , 77 ]. As previously reported in the same study population [ 78 ], T1DM patients displayed low 25(OH)D serum levels compared to healthy controls (15.3 ± 7.0 vs. 17.9 ± 9.3 ng/mL), but the difference was not significant ( p > 0.05).…”

Diabetes pharmacotherapy and effects on the musculoskeletal system

“…Instead, elevated fracture risk is attributed to secondary deficits in the microarchitecture and in the material properties of the bone tissue, along with pathophysiological and genetic factors intrinsic to diabetes itself . Variables inherent to both T1D and T2D, including chronic hyperglycemia and glycemic variation, tissue‐specific accumulation of advanced glycation end‐products (AGEs), dysregulation of insulin‐like growth factor 1 (IGF‐1) bioavailability, variable insulin exposure (endogenous or exogenous), enhanced oxidative stress, changes in bone mineral and vitamin D homeostasis, and regional diabetic microvascular disease, undoubtedly all impact the skeletal quality in diabetes . Added to these variables is an increased propensity to falling, whether attributable to acute hypoglycemia, peripheral neuropathy, decreased visual acuity, or postural instability .…”

Bone health in type 1 diabetes: focus on evaluation and treatment in clinical practice

“…In rat model of T1D, low femoral BMD has improved significantly after treatment with 1α-hydroxyvitamin D3 [32]. Nevertheless, since vitamin D deficiency is related to mineralization defects and increased PTH levels [56,57], the correction of vitamin D deficit state seems to be crucial.…”

“…Moreover, the low levels of insulin-like growth factor-1 (IGF-1) [19,20,[28][29][30][31] and vitamin D [32], which also usually accompany diabetes, may be additional factors responsible for poor bone health (see Fig. 1).…”