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. 2020 Nov 23;7(4):185.
doi: 10.3390/vetsci7040185.

Impact of Dehydroepiandrosterone (DHEA) on Bone Mineral Density and Bone Mineral Content in a Rat Model of Male Hypogonadism

Hussein F Sakr  1   2 , Abdelaziz M Hussein  2 , Elsayed A Eid  3 , Ammar Boudaka  1 , Lashin S Lashin  2   4
Affiliations

Impact of Dehydroepiandrosterone (DHEA) on Bone Mineral Density and Bone Mineral Content in a Rat Model of Male Hypogonadism

Hussein F Sakr et al. Vet Sci. .

Abstract

Objectives: The present study examined the effect DHEA (dehydroepiandrosterone) on bone mineral content (BMC) and bone mineral density (BMD) and biomarkers of bone remodeling in orchidectomized male rats.

Material and methods: A total of 32 male rats were divided equally into four groups (n = 8): (i) control group (C), (ii) control treated with DHEA (Control + DHEA), (iii) orchidectomized (ORCH) group that underwent bilateral orchidectomy and (iv) orchidectomized (ORCH) rats treated with DHEA (ORCH+DHEA). DHEA treatment started 4 weeks after orchidectomy and continued for 12 weeks. After 12 weeks the bone mineral density (BMD) and bone mineral content (BMC) were assayed in the tibia and femur of the right hind limb of each rat. We also measured the serum levels of the bone turnover markers deoxypyridinoline (Dpd), N-telopeptide of type I collagen (NTx), alkaline phosphatase (ALP), tartrate-resistant acid phosphatase 5b (TRAP-5b) and osteocalcin (OC) as well as receptor activator of nuclear factor kappa B (RANK) and osteoprotegerin (OPG).

Results: Orchidectomy in rats caused significant reduction in BMD, BMC, serum levels of testosterone, PTH (parathyroid hormone), OPG, OC and ALP with significant rise in serum levels of TRAP-5B, RANK, Dpd and NTx1 (p < 0.05). On the other hand, DHEA therapy for 12 weeks caused significant improvement in all studied parameters except NTx1 (p < 0.05).

Conclusions: DHEA corrected hypogonadism-induced osteoporosis in male rats probably via inhibiting osteoclastogenesis, stimulating the activity of osteoblasts and stimulating the secretion of PTH and testosterone.

Keywords: ALP; DHEA; OPG; RANK; TRAP-5B; osteocalcin; osteoporosis.

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Conflict of interest statement

Authors declared that there are no conflicts of interest.

Figures

Figure 1
Figure 1
Effect of orchidectomy and DHEA (dehydroepiandrosterone) treatment on the serum levels of (A) testosterone and (B) parathyroid hormone levels. Data were expressed as mean ± SD of 8 rats. *: p < 0.05 versus control, #: p < 0.05 versus control + DHEA, ∆: p < 0.05 versus ORCH (orchidectomized rats).
Figure 2
Figure 2
Effect of orchidectomy and DHEA treatment on (A) bone mineral density (BMD) and (B) bone mineral content (BMC) of the tibia. Representative samples of BMC and BMD from (C) control group, (D) control + DHEA, (E) ORCH and (F) ORCH + DHEA groups. Data were expressed as mean ± SD of 8 rats. *: p < 0.05 versus control, #: p < 0.05 versus control + DHEA, ∆: p < 0.05 versus ORCH.
Figure 3
Figure 3
Effect of orchidectomy and DHEA treatment on serum levels of (A) OPG and (B) RANK. Data were expressed as mean ± SD of 8 rats. *: p < 0.05 versus control, #: p < 0.05 versus control + DHEA, ∆: p < 0.05 versus ORCH. ORCH: orchidectomy, OPG: osteoprotegrin; RANK: receptor activator of nuclear factor kappa B.
Figure 4
Figure 4
Effect of orchidectomy and DHEA treatment on serum level of on bone resorption markers (A) DPD, (B) TRAP-5b and (C) NTXI. Data were expressed as mean ± SD of 8 rats. *: p < 0.05 versus control, #: p < 0.05 versus control + DHEA, ∆: p < 0.05 versus ORCH. ORCH: orchidectomy, Dpd: deoxypyridinoline; NTXI: N-telopeptide of type I collagen; TRAP-5b: tartrate-resistant acid phosphatase 5b.
Figure 5
Figure 5
Effect of orchidectomy and DHEA treatment on serum level of bone formation markers (A) OC and (B) ALP. Data were expressed as mean ± SD of 8 rats.*: p < 0.05 versus control, #: p < 0.05 versus control + DHEA, ∆: p < 0.05 versus ORCH. ORCH: orchidectomy, OC: osteocalcin, ALP: alkaline phosphatase.
Figure 6
Figure 6
Histopathological examination using H&E of proximal metaphysis of the tibia from different groups. The specimens from control group showing a network of trabeculae of cancellous bone with osteocytes within their lacunae within bone trabeculae (black circles) (200×) (A), from ORCH group showing loss of trabecular bone with bone marrow spaces (BM) and few osteoblasts (blue arrows) appear rimming the endosteal surface and (200×) (B,C) and from DHEA + ORCH group showing normal trabecular bone architecture with osteoblasts at endosteal surface (200×) (D).
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