Thyroid-stimulating hormone exerts both antiresorptive and anabolic effects on bone remodeling in aged ovariectomized rats and thyroid stimulating hormone-receptor null mice, supported by clinical results demonstrating that low thyroid-stimulating hormone level is associated with increased bone loss. To further explore the effect of thyroid-stimulating hormone on bone metabolism we introduced here a rat model with removed thyroid and parathyroid glands to obtain low serum concentrations of thyroid and parathyroid hormone, calcitonin and 1,25(OH)2D3. Surgery resulted in hypocalcemia, low parathyroid and thyroid hormone, 1,25(OH)2D3, C-telopeptide, and osteocalcin serum level. Intermittent administration of thyroid-stimulating hormone resulted in a further decrease of serum calcium and decreased level of serum C-telopeptide due to the suppression of bone resorption, while in the same animals osteocalcin in serum was higher indicating an increased bone formation rate. A combination of thyroid-stimulating hormone and 1,25(OH)2D3 significantly increased the serum Ca2+, C-telopeptide and serum osteocalcin values. MicroCT analyses of the distal femur and proximal tibia showed that rats treated with 1,25(OH)2D3 alone or in a combination with thyroid-stimulating hormone had an increased trabecular bone volume, and enhanced trabecular bone quality. Biomechanical testing of the trabecular bone showed an increased maximal load for 105% and 235%, respectively, in rats treated with 1,25(OH)2D3 alone, or in a combination with thyroid-stimulating hormone. We suggest that thyroid-stimulating hormone independently of calciotropic hormones suppressed bone resorption and stimulated bone formation, while in combination with 1,25(OH)2D3 acted synergistically on bone formation resulting in an increased bone volume.

A., Drača N., Kufner V., Trkulja V., Grgurević L., Vukičević S. (2014 To answer this question we examined effects of systemically administered BMP2 and 7 on bone in a newly developed rat model with low level of calciotropic hormones.Methods: Removal of thyroid and parathyroid glands (TPTx) in rats resulted in decreased level of calciotropic hormones and a subsequent bone loss assessed by microCT and measurement of serum bone formation and resorption markers, including osteocalcin, Ctelopeptide, osteoprotegerin and RANKL. Results were complemented with in vitro studies on osteoblast and osteoclast activity by both BMP2 and 7. The doses used have been calculated from published pharmacodynamic (PD) and bioavailability results from preclinical BMP2 and 7 studies.Results: TPTx resulted in bone loss which was restored by systemic administration of 10-70 µg/kg of BMP2 and 10-250 µg/kg of BMP7. BMP2 showed a higher capacity for enhancing trabecular microarchitecture, while BMP7 augmented trabecular thickness. In vitro experiments revealed that BMP2 and 7, when uncoupled, increased the number and activity of both osteoblasts and osteoclasts.Conclusions: Surprisingly, both BMP2 and 7 showed an increased bone volume in an in vivo environment of low calciotropic hormones. Locally administered BMP2 and 7 from bone devices might become partially available in circulation but will not mediate a systemic bone loss.

This study confirmed the possibility of good prenatal diagnosis of skeletal dysplasias present among Qatar population. Diagnosis based on ultrasound assessment will improve by adding molecular techniques with positive impact on prenatal care.

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