Histomorphometric Evaluation of the Recovering Effect of Human Parathyroid Hormone (1–34) on Bone Structure and Turnover in Streptozotocin-Induced Diabetic Rats

Abstract

The purpose of this study was to determine whether human parathyroid hormone (h-PTH) enhances trabecular bone mass and connectivities that were reduced by streptozotocin (STZ)-induced diabetes in rats. Seven-month-old female Wistar rats were injected with STZ or its vehicle intraperitoneally. All vehicle-injected normal controls were sacrificed 0, 4, 6, 8, 12, 14, and 16 weeks after injection, and one-third of the STZ-injected rats were sacrificed as the baseline controls 4, 6, and 8 weeks after the injection. Eight-week h-PTH (6. 0 microg/kg, 6 times a week) or its vehicle treatment by subcutaneous injection for residual diabetic rats was started 4, 6, or 8 weeks after the STZ injection. The rats' proximal right tibiae were processed for undecalcified Villanueva bone staining sections for bone histomorphometry. Furthermore, changes in trabecular connectivities were determined by node-strut analysis. The decreased cancellous bone volume (BV/TV) and turnover in diabetic rats were recovered in all PTH-treated groups. In node-strut analysis, the node-related parameters (N.Nd/TV, NdNd/TV) were significantly increased by PTH when it was administered 4 weeks after STZ injection but were not increased when administration was started after 6 weeks. The results indicated that PTH enhanced bone turnover and bone mass but not trabecular connectivity in the late stage of diabetes in rats. Early treatment of osteoporosis is important in preventing fractures caused by decreased bone strength resulting from decreased trabecular connectivity.

Effects of h-PTH on cancellous bone mass, connectivity, and bone strength in ovariectomized rats with and without sciatic-neurectomy

“…We previously reported that in rats in the late stage of diabetes, there is a critical limit on trabecular connectivity below which PTH could not restore connectivity [31]. In the present study, the values of trabecular thickness and bone formation rate were increased by PTH in the late post-surgical stage in OVX + NX rats.…”

“…The rats were pairfed and allowed free access to water and standard food (CE-2, CLEA Japan Inc., Tokyo, Japan), containing 1.14% calcium, 1.06% phosphorus, and 250 IU vitamin D3 per 100 g, as previously described [1,20,31]. Osteopenia was induced by bilateral ovariectomy, with or without bilateral sciatic neurectomy (OVX or OVX + NX), which was accomplished by resecting a 10 mm segment of the nerve posterior to the hip joint.…”

“…Bone histomorphometry and node-strut analysis were performed with a semiautomatic graphic system as previously described [1, 20,31]. Measurements were obtained in areas 390 pm from the lowest point of the growth plate-metaphyseal junctions in the caudal direction.…”

The Effect of Type 1 Diabetes Mellitus on the Craniofacial Complex

“…In addition to this, insulin may exert synergistic effects with other anabolic agents in bone, such as parathyroid hormone (PTH) (Thomas et al, 1998;Thrailkill et al, 2005). An animal model of T1DM has frequently demonstrated alteration in bone turnover, retarded growth, increased concentration of PTH, and reduced concentration of 1,25-dihydroxivitamin D (Duarte et al, 2005;Tsuchida et al, 2000). The effects of PTH on the bones are complex; it stimulates resorption or bone formation depending on the concentration used, the duration of the exhibition, and the administration method (Duarte et al, 2005;Toromanoff et al, 1997;Tsuchida et al, 2000).…”

Intermittent Administration of Human Parathyroid Hormone before Osteosynthesis Stimulates Cancellous Bone Union in Ovariectomized Rats

“…PTH can increase bone mass in osteoporotic humans and rats with osteopenia induced by various causes (Tsuchida et al 2000;Tsuchida et al 2001;Kasukawa et al 2004;Miyakoshi 2004). Several studies have reported that intermittent administration of human PTH also enhances fracture healing of cortical bones such as the shaft of the femur or tibia after surgical intervention in animals (Andeassen et al 1999;Holzer et al 1999;Nakazawa et al 2005), even in an osteoporotic animal model (Jahng and Kim 2000).…”