Effects of Parathyroid Hormone on Bone Mass, Bone Strength, and Bone Regeneration in Male Rats With Type 2 Diabetes Mellitus

Abstract

Type 2 diabetes mellitus (T2DM) is associated with increased skeletal fragility and impaired fracture healing. Intermittent PTH therapy increases bone strength; however, its skeletal and metabolic effects in diabetes are unclear. We assessed whether PTH improves skeletal and metabolic function in rats with T2DM. Subcritical femoral defects were created in diabetic fa/fa and nondiabetic +/+ Zucker Diabetic Fatty (ZDF) rats and internally stabilized. Vehicle or 75 μg/kg/d PTH(1-84) was sc administered over 12 weeks. Skeletal effects were evaluated by μCT, biomechanical testing, histomorphometry, and biochemical markers, and defect regeneration was analyzed by μCT. Glucose homeostasis was assessed using glucose tolerance testing and pancreas histology. In diabetic rats, bone mass was significantly lower in the distal femur and vertebrae, respectively, and increased after PTH treatment by up to 23% in nondiabetic and up to 18% in diabetic rats (P < .0001). Diabetic rats showed 23% lower ultimate strength at the spine (P < .0005), which was increased by PTH by 36% in normal and by 16% in diabetic rats (P < .05). PTH increased the bone formation rate by 3-fold in normal and by 2-fold in diabetic rats and improved defect regeneration in normal and diabetic rats (P < .01). PTH did not affect serum levels of undercarboxylated osteocalcin, glucose tolerance, and islet morphology. PTH partially reversed the adverse skeletal effects of T2DM on bone mass, bone strength, and bone defect repair in rats but did not affect energy metabolism. The positive skeletal effects were generally more pronounced in normal compared with diabetic rats.

Endocrine role of bone: recent and emerging perspectives beyond osteocalcin

“…PTH had no effect on body weight, glucose tolerance or pancreatic islet morphology in both groups, despite PTH therapy resulting in bone anabolic effects and bone defect repair. Unfortunately, the authors were unable to detect undercarboxylated OC; however, they reported no change in carboxylated OC between vehicle and PTH-treated non-diabetic and diabetic rats (Hamann et al 2014). These results are surprising as intermittent therapy is known to increase serum levels of OC (Neer et al 2001, Greenspan et al 2007.…”

Effect of intermittent PTH treatment on plasma glucose in osteoporosis: A randomized trial

“…on the other hand a recent animal study by Hamann et al (37), shows no effect of iPTH on rat body weight.…”

“…Some studies show that uOC influences β cells proliferation and activity (2,21,22), whereas others do not (37).…”

Quantitative analysis of bone and soft tissue by micro-computed tomography: applications to ex vivo and in vivo studies

“…6 The scan region ranges between 0.1 and0.7 mm for both mice and rats. 2,11,[14][15][16] If using a percentage of the long bone length, 10-15% of the total length is common. 6,17 In this case, it is recommended to scan a larger region than needed and to calculate a subregion in the analysis phase.…”

“…The majority of studies on the vertebra examine the entire vertebral body. 11,14,15,19,20 Alternatively, some researchers have specified a volume (for example, 2 mm) centred at the midline, 8 or they have used the growth plate as a landmark. 7,21,22 As the mid-region is sparsely populated with trabecular bone, and the bone volume density is inhomogeneously distributed throughout the vertebral body, it is recommended to analyse the entire volume unless the study question gives cause to focus on a specific subvolume.…”