Effects of parathyroid hormone on bone mass, bone strength, and bone regeneration in male rats with type 2 diabetes mellitus.
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.
Department of Orthopedics (C.H., K.-P.G.) and Division of Endocrinology, Diabetes, and Metabolic Bone Diseases, Department of Medicine III (A.-K.P., M.B., M.R., S.R.B., B.L., L.C.H.), Dresden Technical University Medical Center, Dresden, Germany; Section Molecular Imaging, Department of Radiology, MOIN CC (G.M.C., C.-C.G.), Kiel, Germany; Paul Langerhans Institute Dresden, German Center for Diabetes Research (S.R.B., B.L.), Dresden, Germany; Max Bergmann Center of Biomaterials (R.B.), Technical University, Dresden, Germany; Institute of Biomechanics (G.H., M.M.M.), TUHH Hamburg University of Technology, Hamburg, Germany; Center for Regenerative Therapies Dresden, Germany (K.-P.G., S.R.B., B.L., L.C.H.).
Christine
C
Hamann
Ann-Kristin
AK
Picke
Graeme M
GM
Campbell
Mariya
M
Balyura
Martina
M
Rauner
Ricardo
R
Bernhardt
Gerd
G
Huber
Michael M
MM
Morlock
Klaus-Peter
KP
Günther
Stefan R
SR
Bornstein
Claus-C
CC
Glüer
Barbara
B
Ludwig
Lorenz C
LC
Hofbauer
D000818:Animals; D001696:Biomechanical Phenomena; D001835:Body Weight; D015519:Bone Density / Q000187:drug effects*; D001861:Bone Regeneration / Q000187:drug effects*; D001842:Bone and Bones / Q000187:drug effects* / Q000473:pathology / Q000648:ultrastructure; D048909:Diabetes Complications / Q000188:drug therapy; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000503:physiopathology*; D004195:Disease Models, Animal; D005269:Femur / Q000187:drug effects / Q000473:pathology; D017102:Fracture Healing / Q000187:drug effects; D005947:Glucose / Q000378:metabolism; D005951:Glucose Tolerance Test; D006706:Homeostasis; D008297:Male; D010179:Pancreas / Q000473:pathology; D010281:Parathyroid Hormone / Q000378:metabolism / Q000627:therapeutic use*; D051381:Rats; D011924:Rats, Zucker; D055114:X-Ray Microtomography
D010281:Parathyroid Hormone; D005947:Glucose