Low Bone Density with Normal Bone Turnover in Ovariectomized and Streptozotocin-Induced Diabetic Rats

Abstract

Diabetes and estrogen deficit are known causes of osteopenia, diabetes being associated with a low bone turnover and estrogen deficit with a high bone turnover. In the present work, we studied the effect of combined ovariectomy and diabetes on bone mineral content (BMC) and bone mineral density (BMD) and several bone markers in the rat. Four groups of rats were studied: control (C), ovariectomized (O), diabetic (D), and ovariectomized and diabetic (DO). Twelve weeks after starting the experiments, BMC and BMD of the first six lumbar vertebrae were measured; a bone formation marker (BGP) and a bone resorption marker (free collagen cross-links, PYD) were also analyzed. Diabetic rats showed diminished gain in bone mass, BMC (D: 0.417 +/- 0.028 g, DO: 0.422 +/- 0.020 g) and BMDs (D: 0.171 +/- 0.006 g/cm2, DO: 0.174 +/- 0.006 g/cm2) both being significantly (P < 0.001) lower than those of control (C: BMC 0.727 +/- 0.024 g and BMD 0.258 +/- 0.004 g/cm2) and ovariectomized (O: BMC 0.640 +/- 0.044 g and BMD 0.240 +/- 0.009 g/cm2) groups. Moreover, the BMC and BMD of the C group were significantly (P < 0.05) higher than that of the O group. BGP and PYD levels were significantly (P < 0.01) higher in the O group (BGP: 138.2 +/- 16.8 ng/ml, PYD: 270.2 +/- 17.8 nM/mM) than those found in the control rats (BGP: 44.7 +/- 4.8 ng/ml, PYD: 165.6 +/- 12.5 nM/mM); the D group showed significantly (P < 0.01) lower values (BGP: 27.4 +/- 14.6 ng/ml, PYD: 55.0 +/- 7.4 nM/mM) than those of the control group. The DO group showed similar levels (BGP: 43.4 +/- 5.1 ng/ml, PYD: 146.7 +/- 14.6 nM/mM) to those found in the C group. Although bone marker levels in the O and D groups were in accordance with those expected in these situations, in the DO group the corresponding levels are apparently "normal." Also, the decrease of gain in bone mass observed after combining estrogen deficit and diabetes (DO group) did not seem to be more marked than that caused by diabetes alone.

Hyperglycemia Diverts Dividing Osteoblastic Precursor Cells to an Adipogenic Pathway and Induces Synthesis of a Hyaluronan Matrix That Is Adhesive for Monocytes

“…These events include a decrease in osteoblast differentiation/maturation (1,55,56); an increase in adipocyte differentiation (10,15,55); an increase in monocyte/macrophage activation (57); an increase in bone inflammation (55, 57); and a decrease or no change in osteoclast number, erosion depth, and erosion surface (12,13,55,58). However, the mechanisms underlying diabetic bone mineral loss are still unclear.…”

“…In diabetic patients, decreased osteoblast function is thought to be associated with a defect of osteocyte maturation on the basis of normal serum levels of procollagen peptide, an early osteoblast marker, and decreased serum levels of osteocalcin, a late-stage marker of osteoblast maturation (10,11). The decrease in serum osteocalcin is even more pronounced in diabetic rat models (5,(12)(13)(14). These data suggest that a decrease in osteoblast number, function, and/or maturation may be a contributor(s) to bone loss in diabetes (10).…”

Effects of Ovariectomy on Bone Metabolism and Bone Mineral Density in Spontaneously Diabetic Torii-Leprfa Rats

“…1B and 1C). Herrero et al also showed no effect of OVX on serum glucose levels in streptozotocininduced diabetic rats [4]. These data suggest that OVX hardly affects glucose metabolism.…”

“…High glucose condition decreased cell proliferation and osteocalcin secretion in human osteoblast-like MG-63 cells [5]. Bone loss associated with low bone formation was observed in rats with diabetes [4,16]. On the other hand, urine DPD levels were higher in SDT-fa/fa rats than in control rats 15-30 weeks after surgery (Table 1).…”

“…Ovariectomy (OVX) in rats is widely used as an appropriate model for postmenopausal osteoporosis in humans [8]. OVX has no effect on BMD in rats with type 1 diabetes [4], but its effect on BMD in rats with type 2 diabetes has not been reported.…”