Mechanical Vibration Associated With Intermittent PTH Improves Bone Microarchitecture in Ovariectomized Rats.

INTRODUCTION: Intermittent 1-34 parathyroid hormone (iPTH) administration, a bone-forming treatment, is widely used as a therapy for severe osteoporosis. It can only be used for a maximum of 24 mo and must be followed by an antiresorptive drug to retain the new formed tissue. Mechanical load, in the form of low-intensity and high-frequency vibration, has received considerable attention due to its ability to prevent bone loss. AIM: To investigate the ability of whole body mechanical vibration (MV) to potentiate the anabolic effects of iPTH and to inhibit bone resorption following discontinuation of iPTH treatment in estrogen-deficient rats. METHODOLOGY: Fifty-four 6-month-old female Wistar rats were ovariectomized (OVX) or sham-operated. After 5 mo, they were divided into 7 groups: Sham - non-OVX; Control - OVX, vehicle for 60 d; MV - OVX, submitted to MV for 60 d; PTH60d - OVX, injected with iPTH for 60 d; PTH+MV - OVX, injected with iPTH combined with MV for 60 d; PTH30d - OVX, injected with iPTH for 30 d, and untreated for 30 d; PTH30d/MV30d - OVX, injected with iPTH for 30 d, followed by MV for 30 d. Bone mineral density (BMD) and body composition (lean mass and fat) were evaluated at OVX (T0), the beginning (T1), and at the end (T2) of treatments by dual X-ray absorptiometry (DXA). Femurs were processed for histomorphometry (bone volume - BV/TV and cortical thickness - Ct.Th) and tibias for biomechanical test. RESULTS: Body composition and BMD were similar among the groups at T0. In T2, MV presented higher fat than other groups (except PTH60d) and PTH30d/MV30d showed greater lean mass than Control. At T1, Sham presented the highest BMD, but between T1 vs T2 there was an increase in all iPTH-treated groups. At T2, BMD was higher in PTH60d and PTH+MV than in the Control and MV groups. The highest BV/TV was observed in the PTH+MV group, followed by PTH60d. Cortical thickness was increased in PTH60d and PTH+MV compared to Sham. Vibration applied post-iPTH (PTH30d/MV30d) improved the force at failure in tibias when compared to Sham and Control groups. CONCLUSION: MV potentiated iPTH anabolic effects in cancellous bone; however, MV was unable to maintain bone mass after stopping iPTH in ovariectomized rats.

Modifications in bone matrix of estrogen-deficient rats treated with intermittent PTH.

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.