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Updated: Aug 18, 2026
Generation of Hypoparathyroid Rats via Carbon-Nanoparticle-Assisted Parathyroidectomy
Published on: July 14, 2023
Intermittently administered parathyroid hormone 1-34 reverses bone loss and structural impairment in orchiectomized
Yankel Gabet1, David Kohavi, Ralph Müller
1Bone Laboratory, The Hebrew University of Jerusalem, Jerusalem, Israel.
Abstract:
Male osteoporosis is emerging as a central theme in bone research. As in females, hypogonadism appears as a principal risk factor in men that leads to bone loss and increased fracture incidence. Intermittently administered parathyroid hormone (PTH) reverses bone loss in sex hormone-deprived women and female animals and increases bone mass in elderly men and normal male animals. This study was carried out to assess whether the PTH anabolic activity is also effective in adult castrated males and to gain insight into the underlying tissue processes. Bilateral orchiectomy (ORX) or sham-ORX was performed in 13-week old rats. Five weeks later, the ORX rats were treated intermittently with human PTH(1-34), 80 microg/kg/day or vehicle for 6 weeks. Femora were evaluated by quantitative micro-computed tomography followed by dynamic histomorphometry. The trabecular bone volume density showed 40% and 56% ORX-induced loss in the distal metaphysis at 6 weeks and 12 weeks post-ORX, respectively. PTH(1-34) induced supraphysiologic recovery of this bone loss (155% recovery) consequent to a vast increase in trabecular thickness (174% over sham-ORX controls) and a partial reversal (62%) of the decrease in trabecular number. As compared with the results in 12-week, orchiectomized vehicle-administered rats, the PTH(1-34) treatment induced a significant decrease in osteoclast number (20%) and twofold increase in bone formation rate. While ORX did not affect the femoral diaphysis, PTH(1-34) induced marked cortical thickening via the stimulation of endosteal mineral appositional rate (154% over ORX rats). These data portray PTH(1-34) as a highly potent bone anabolic agent in adult ORX rats, mainly by increasing both the trabecular and cortical thicknesses through its effect on osteoblasts and osteoclasts. The adult ORX rat is useful for investigating the processes involved in bone anabolic activity in castrated osteoporotic males and for the development of bone anabolic agents for treating this condition.
Insights
Parathyroid hormone (PTH) effectively reverses bone loss in castrated male rats. This study shows PTH increases bone thickness and formation, offering potential for treating male osteoporosis.
Area of Science:
- Bone biology and endocrinology
- Osteoporosis research
- Pharmacological interventions for bone disease
Background:
- Male osteoporosis is a growing concern, with hypogonadism as a key risk factor leading to bone loss.
- Intermittent parathyroid hormone (PTH) administration has shown efficacy in reversing bone loss in females and increasing bone mass in elderly males.
Purpose of the Study:
- To evaluate the anabolic efficacy of PTH in adult castrated male rats.
- To investigate the underlying tissue-level mechanisms of PTH's action in this model.
Main Methods:
- Adult male rats underwent bilateral orchiectomy (ORX) or sham surgery.
- ORX rats received intermittent human PTH(1-34) or vehicle treatment.
- Femoral bone was analyzed using micro-computed tomography and histomorphometry.
Main Results:
- Orchiectomy induced significant trabecular bone loss, which was substantially recovered by PTH treatment (155% recovery).
- PTH increased trabecular thickness and bone formation rate while decreasing osteoclast number.
- PTH also stimulated cortical thickening in the femoral diaphysis.
Conclusions:
- Human PTH(1-34) is a potent bone anabolic agent in adult castrated male rats.
- PTH increases bone mass by enhancing trabecular and cortical bone thickness through effects on osteoblasts and osteoclasts.
- The adult castrated rat model is valuable for studying bone anabolic therapies for male osteoporosis.
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