Modifications in Bone Matrix of Estrogen-Deficient Rats Treated with Intermittent PTH

Abstract

Bone matrix dictates strength, elasticity, and stiffness to the bone. Intermittent parathyroid hormone (iPTH), a bone-forming treatment, is widely used as a therapy for osteoporosis. We investigate whether low doses of intermittent PTH (1-34) change the profile of organic components in the bone matrix after 30 days of treatment. Forty 6-month-old female Wistar rats underwent ovariectomy and after 3 months received low doses of iPTH administered for 30 days: daily at 0.3 µg/kg/day (PTH03) or 5 µg/kg/day (PTH5); or 3 times per week at 0.25 µg/kg/day (PTH025). After euthanasia, distal femora were processed for bone histomorphometry, histochemistry for collagen and glycosaminoglycans, biochemical quantification of sulfated glycosaminoglycans, and hyaluronan by ELISA and TUNEL staining. Whole tibiae were used to estimate the bone mineral density (BMD). Histomorphometric analysis showed that PTH5 increased cancellous bone volume by 6% over vehicle-treated rats. In addition, PTH5 and PTH03 increased cortical thickness by 21% and 20%, respectively. Tibial BMD increased in PTH5-treated rats and this group exhibited lower levels of chondroitin sulfate; on the other hand, hyaluronan expression was increased. Hormonal administration in the PTH5 group led to decreased collagen maturity. Further, TUNEL-positive osteocytes were decreased in the cortical compartment of PTH5 whereas administration of PTH025 increased the osteocyte death. Our findings suggest that daily injections of PTH at low doses alter the pattern of organic components from the bone matrix, favoring the increase of bone mass.

Different doses of strontium ranelate and mechanical vibration modulate distinct responses in the articular cartilage of ovariectomized rats

“…Animal models of OA have often been used to study the pathogenesis of the disease as well as therapeutic treatment efficacy 27 . Ovariectomy (OVX) is an established procedure that provides a useful model to simulate the hormonal condition of postmenopausal women and is frequently used to simultaneously reproduce a postmenopausal model of osteoporosis 18,28 and OA 2,29 .…”

Estrogen therapy associated with mechanical vibration improves bone microarchitecture and density in osteopenic female mice

“…In this study, we investigated the effects of ET associated with low-intensity and high-frequency MV on bone tissue of osteopenic female mice, a classic animal model of postmenopausal osteoporosis (Nakamura et al 2007;Li et al 2010;Syed et al 2010;Ozturan et al 2011;Chan et al 2013;Florencio-Silva et al 2013;Santos et al 2014;Pacheco-Costa et al 2015).…”

“…Collagen is the main component of the organic bone matrix, and altered collagen is associated with bone fragility (Pacheco-Costa et al 2015). The degree of maturation of collagen fibers is related to the thickness and pattern of color of their birefringence (Montes, 1996).…”

“…; Pacheco‐Costa et al. ). The sections were deparaffinized, rehydrated and incubated with 0.2% aqueous phosphomolybdic acid for 10 min to render the cytoplasm colorless, and then stained with 0.1% solution of Sirius red diluted in saturated aqueous picric acid for 90 min.…”

“…Bone sections were stained using a modified picrosirius red (Sigma Chemical) technique previously described, and the birefringence of the collagen fibers was evaluated in the distal femur at 190 lm below the lowest point of the growth plate (Junqueira et al 1979;Florencio-Silva et al 2013;Santos et al 2014;Pacheco-Costa et al 2015). The sections were deparaffinized, rehydrated and incubated with 0.2% aqueous phosphomolybdic acid for 10 min to render the cytoplasm colorless, and then stained with 0.1% solution of Sirius red diluted in saturated aqueous picric acid for 90 min.…”