Bone Geometry, Quality, and Bone Markers in Children with Type 1 Diabetes Mellitus

Abstract

Adults with Type 1 diabetes mellitus show a high risk of bone fracture, probably as a consequence of a decreased bone mass and microarchitectural bone alterations. The aim of the study was to investigate the potential negative effects of type 1 diabetes on bone geometry, quality, and bone markers in a group of children and adolescents. 96 children, mean age 10.5 ± 3.1 years, agreed to participate to the study. Bone geometry was evaluated on digitalized X-rays at the level of the 2nd metacarpal bone. The following parameters were investigated and expressed as SDS: outer diameter (D), inner diameter (d), cortical area (CA), and medullary area (MA). Bone strength was evaluated as Bending Breaking Resistance Index (BBRI) from the geometric data. Bone turnover markers (PINP, CTX-I, and BAP), sclerostin, Dkk-1, PTH, and 25OH-Vitamin D were also assessed. A group of healthy 40 subjects of normal body weight and height served as controls for the bone markers. D (- 0.99 ± 0.98), d (- 0.41 ± 0.88), CA (- 0.85 ± 0.78), and MA (- 0.46 ± 0.78) were all significantly smaller than in controls (p < 0.01). BBRI was significantly lower (- 2.61 ± 2.18; p < 0.0001). PTH, PINP, and BAP were higher in the diabetic children. Multiple regression analysis showed that CA and D were influenced by insulin/Kg/day and by BMI, while d was influenced by PINP only. Type 1 diabetic children show smaller and weaker bones. The increased bone turnover could play a key role since it might amplify the deficit in bone strength associated with the inadequate osteoblastic activity caused by the disease itself.

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

“…Our patients with T1DM showed reduced levels of 25(OH)D compared with the healthy controls. Consistently, in other studies it has been reported that patients with T1DM displayed vitamin D deficiency [ 11 , 20 , 28 , 47 , 54 , 59 ], and that insulin gene expression in pancreatic β -cells may also be modulated by vitamin D [ 20 , 35 , 37 , 76 ]. Vitamin D also modulates muscle and bone-derived hormones, hormones, including GH-IGF-1 axis and sex hormones, facilitating cross-talk between these tissues [ 77 ].…”

“…Our results also demonstrate reduced BMC or BMD Z-scores and an impairment of the relationship between the fat and muscle tissue. Several previous studies also investigated this association and found similar results [ 16 – 18 , 20 , 21 , 29 , 44 – 46 , 58 , 59 ]. Our observations of reduced relative bone strength of T1DM patients, and more so in the poor metabolic control patients, have led us to speculate that maintaining such status may be associated with increased risk of fractures later in life.…”

Bone turnover markers in children and adolescents with type 1 diabetes—A systematic review

“…In the end, 26 studies matched our criteria and were included; 20 cross‐sectional studies and six prospective cohort studies . One cohort by Saggese et al was an intervention cohort study, but since we did not use postintervention data, baseline data were used in the pooled meta‐analysis.…”

“…Three studies did not include control groups . Most studies made it clear that the included participants and controls had no concurrent diseases, and only two articles did not state this . Seven studies did not state whether the blood tests were drawn in a fasting state and only six studies reported on blood glucose levels when tested, ranging from 9.3 to 16.52 mmol/L …”

“…Some of these factors are analyzed in the included studies, together with OCN, CTX and P1NP, and includes vitamin D and parathyroid hormone (PTH). These well‐known influencers of calcium metabolism and bone health showed inconsistent results with levels equal to controls in most studies for both vitamin D and parathyroid hormone . However, low and high parathyroid hormone levels were reported along with high and low vitamin D levels.…”