The Relationship Between Bone and Reproductive Hormones Beyond Estrogens and Androgens

Mills, Edouard; Yang, Lisa; Nielsen, Morten Holtegaard; Kassem, Moustapha; Dhillo, Waljit S.; Comninos, Alexander

doi:10.1210/endrev/bnab015

Cited by 64 publications

(50 citation statements)

References 255 publications

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“…Reproductive hormones are a known factor for aging- and menopause-related bone loss 51 , 52 . In postmenopausal women, serum estradiol (E2) is drastically reduced while follicle-stimulating hormone (FSH) is increased 53 – 55 .…”

Section: Discussionmentioning

confidence: 99%

Micro-computed tomography assessment of bone structure in aging mice

Shim

Iwaya

Ambrose

et al. 2022

Sci Rep

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High-resolution computed tomography (CT) is widely used to assess bone structure under physiological and pathological conditions. Although the analytic protocols and parameters for micro-CT (μCT) analyses in mice are standardized for long bones, vertebrae, and the palms in aging mice, they have not yet been established for craniofacial bones. In this study, we conducted a morphometric assessment of craniofacial bones, in comparison with long bones, in aging mice. Although age-related changes were observed in the microarchitecture of the femur, tibia, vertebra, and basisphenoid bone, and were more pronounced in females than in males, the microarchitecture of both the interparietal bone and body of the mandible, which develop by intramembranous ossification, was less affected by age and sex. By contrast, the condyle of the mandible was more affected by aging in males compared to females. Taken together, our results indicate that mouse craniofacial bones are uniquely affected by age and sex.

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Section: Discussionmentioning

confidence: 99%

Micro-computed tomography assessment of bone structure in aging mice

Shim

Iwaya

Ambrose

et al. 2022

Sci Rep

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“…Since the first identification of the crucial role for kisspeptin in reproductive hormone control, there has emerged a plethora of literature describing its role in other diverse processes from metabolism to behavior ( 21 , 47-51 ). As such, given the immense energy expenditure of human bone remodeling and its close interplay with reproductive hormones ( 25 ), it is unsurprising to find a link emerging between kisspeptin and bone. Indeed recent pivotal work has identified a neuroskeletal axis, whereby inhibiting estrogen signaling in hypothalamic kisspeptin neurons promotes dense strong bones in rodents, independent of circulating estradiol levels ( 52 ).…”

Section: Discussionmentioning

confidence: 99%

“…It is therefore timely that recent data in rodents demonstrate that kisspeptin administration directly promotes osteoblast differentiation in vitro via the kisspeptin receptor (Kiss1r) expressed on rodent osteoblasts ( 24 ). This suggests that kisspeptin may have direct beneficial effects on skeletal homeostasis, independent of its ability to stimulate downstream sex steroid levels via its more established action on the hypothalamic–pituitary–gonadal axis ( 25 ). However, there are no data on the direct effects of kisspeptin on human bone metabolism as yet, and so we aimed to investigate this.…”

mentioning

confidence: 99%

Acute Effects of Kisspeptin Administration on Bone Metabolism in Healthy Men

Comninos

Hansen

Courtney

et al. 2022

The Journal of Clinical Endocrinology &Amp; Metabolism

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Context Osteoporosis results from disturbances in bone formation and resorption. Recent non-human data suggests that the reproductive hormone, kisspeptin, directly stimulates osteoblast differentiation in vitro and thus could have clinical therapeutic potential. However, the effects of kisspeptin on human bone metabolism are currently unknown. Objective To assess the effects of kisspeptin on human bone metabolism in vitro and in vivo. Design In vitro study: Mono- and co-cultures of human osteoblasts and osteoclasts treated with kisspeptin. Clinical study: Randomized, placebo-controlled, double-blind, two-way crossover clinical study in twenty-six men investigating the effects of acute kisspeptin administration (90 minutes) on human bone metabolism, with blood sampling every 30 minutes to +90 minutes. Participants In vitro study: Twelve male blood donors and eight patients undergoing hip replacement surgery. Clinical Study: Twenty-six healthy eugonadal men (age 26.8±5.8 years). Intervention Kisspeptin (versus placebo). Main Outcome Measures Changes in bone parameters and turnover markers. Results Incubation with kisspeptin in vitro increased alkaline phosphatase levels in human bone marrow mesenchymal stem cells by 41.1% (P=0.0022), and robustly inhibited osteoclastic resorptive activity by up to 53.4% (P<0.0001), in a dose-dependent manner. Kisspeptin administration to healthy men increased osteoblast activity, as evidenced by a 20.3% maximal increase in total osteocalcin (P=0.021) and 24.3% maximal increase in carboxylated osteocalcin levels (P=0.014). Conclusions Collectively, these data provide the first human evidence that kisspeptin promotes osteogenic differentiation of osteoblast progenitors and inhibits bone resorption in vitro. Furthermore, kisspeptin acutely increases the bone formation marker osteocalcin but not resorption markers in healthy men, independent of downstream sex-steroid levels. Kisspeptin could therefore have clinical therapeutic application in the treatment of osteoporosis.

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“…18 Other factors such as aging and the associated increase in reactive oxygen species or hormones such as Kisspeptins may interact. 19,20…”

Section: Estrogen Deficiency and Its Effect On The Skeletonmentioning

confidence: 99%

Menopause Hormone Therapy in the Management of Postmenopausal Osteoporosis

Rozenberg¹,

Vandromme²,

Revercez³

et al. 2022

Cancer J

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This narrative review analyzes the customization of menopause hormone therapy (MHT) for osteoporosis prevention and treatment in the context of the patients' age and menopausal age. In short, MHT is indicated in most women suffering from menopause before the age of 45 years except for breast cancer survivors. These women should be treated with MHT until the age of 50 years. For women who have entered menopause at around the age of 50 years, risks associated with MHT are low, and MHT is a safe option, provided there is an indication for it. We suggest that pursuing MHT entails different risks than initiating it, after the age of 60 years. In both cases, advantages and risks should be evaluated. We suggest using risk calculators to assess the magnitude of these risks and choosing regimens that entail the lowest breast and thrombosis risks.

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The Relationship Between Bone and Reproductive Hormones Beyond Estrogens and Androgens

Cited by 64 publications

References 255 publications

Micro-computed tomography assessment of bone structure in aging mice

Micro-computed tomography assessment of bone structure in aging mice

Acute Effects of Kisspeptin Administration on Bone Metabolism in Healthy Men

Menopause Hormone Therapy in the Management of Postmenopausal Osteoporosis

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