oxytocin and Osteoporosis

Osteoporosis and overweight/obesity constitute major worldwide public health burdens. Aging is associated with a decrease in hormonal secretion, lean mass and bone mass, and an increase in fat accumulation. It is established that both obesity and osteoporosis are affected by genetic and environmental factors, bone remodeling and adiposity are both regulated through the hypothalamus and sympathetic nervous system. Oxytocin (OT), belongs to the pituitary hormone family and regulates the function of peripheral target organs, its circulating levels decreased with age. Nowadays, it is well established that OT plays an important role in the control of bone and fat mass and their metabolism. Of note, OT and oxytocin receptor knock out mice develop bone defects and late-onset obesity. Thus OT emerges as a promising molecule in the treatment of osteoporosis and obesity as well as associated metabolic disorders such as type 2 diabetes and cardiovascular diseases. In this review, we will discuss findings regarding the OT effects on bone and fat mass.

Topics: Adipose Tissue; Animals; Bone and Bones; Humans; Mice; Osteoporosis; Oxytocics; Oxytocin

Background and Objectives: Oxytocin (OT) is a neuropeptide hormone which is known for its classical effects in pregnancy and lactation. Recently, growing evidence demonstrated a close relation between OT and bone. The present study aimed to explore the relationship between OT, bone and osteoporosis risk in Chinese adult females. Materials and Methods: in total, 149 adult females were enrolled. The serum OT levels were measured using ELISA kits. Bone mineral density (BMD) and body composition were measured by dual-energy X-ray absorptiometry (DXA). The study subjects were divided into two groups according to their menopause status and then divided into tertiles based on their serum OT level. Results: Serum OT, serum estradiol and BMD at three skeletal sites were significantly higher in the premenopausal group than in the postmenopausal group (p < 0.001, p = 0.008 and p < 0.001, respectively). In the tertile analysis, relative to tertile 1, significant associations were found for tertile 3 for OT levels and higher BMD in the femoral neck and total hip, in both pre- and postmenopausal groups. Using logistic regression analysis, tertile 3 appeared less likely to have low-BMD osteoporosis than tertile 1 (OR = 0.257, 95% CI = 0.073, 0.910). In multivariate stepwise regression analysis, OT and total lean mass were two positive determinants of BMD in the femoral neck and total hip in the premenopausal group (adjusted R2 for the model = 0.232 and 0.199, respectively; both p < 0.001). Conclusion: Our study demonstrated positive associations between serum OT levels and BMD in a Chinese (non-Caucasian) population. OT appeared to be more strongly associated with hip BMD in premenopausal females. These results may suggest a protective role and potential therapeutic use of OT in osteoporosis, especially for premenopausal women.

Topics: Adult; Body Composition; Bone Density; China; Female; Humans; Osteoporosis; Oxytocin

Osteoporosis and sarcopenia are major health issues in postmenopausal women due to their high prevalence and association with several adverse outcomes. However, no biomarkers may be used for screening and diagnosis. The current study investigated potential biomarkers for osteoporosis and/or sarcopenia in postmenopausal women.. A cross-sectional study on 478 healthy community-dwelling postmenopausal women aged 50-90 years was performed. Osteoporosis and sarcopenia were defined according to the World Health Organization (WHO) and Asian Working Group for Sarcopenia (AWGS).. Dehydroepiandrosterone (DHEA) was related to muscle strength (β = 0.19, p = 0.041) and function (β = 0.58, p = 0.004). Follistatin (β = - 0.27, p = 0.01) was related to muscle mass. Oxytocin (β = 0.59, p = 0.044) and DHEA (β = 0.51, p = 0.017) were related to bone mass. After adjusting for age, oxytocin (odds ratio (OR) 0.75; 95% confidence intervals (CI) 0.63-0.98; p = 0.019) was associated with osteoporosis, and DHEA (OR 0.73; 95% CI 0.51-0.96; p = 0.032) and follistatin (OR 1.66; 95% CI 1.19-3.57; p = 0.022) were associated with sarcopenia.. Postmenopausal women with sarcopenia were more likely to have lower DHEA levels and higher follistatin levels, and postmenopausal women with osteoporosis were more likely to have lower oxytocin levels.

Topics: Aged; Aged, 80 and over; Cross-Sectional Studies; Dehydroepiandrosterone; Female; Follistatin; Humans; Middle Aged; Osteoporosis; Oxytocin; Postmenopause; Sarcopenia

The probable positive effects of photobiomodulation therapy (PBMT) and oxytocin (OT) treatments together or alone were evaluated on cell viability along with the changes in the gene expression of Osteocalcin (OC), Osteoprotegerin (OPG), and Runt-related transcription factor 2 (Runx2) levels of sham (healthy)-Bone marrow mesenchymal stem cell(BMMSC) and ovariectomy-induced osteoporosis (OVX)-BMMSC. BMMSC was harvested from healthy and OVX rats and was cultured in osteogenic induction medium (OIM). There were five groups of BMMSCs: (1) sham -BMMSCs; (2) control -OVX-BMMSCs; (3) OT-treated-OVX-BMMSCs; (4) PBMT-treated-OVX-BMMSCs, and (5) OT + PBMT-OVX-BMMSCs. In all 5 groups, BMMSC viability and proliferation as well as gene expression of OC, OPG, and RUNX2 were evaluated. PBMT and PBMT + OT treatments showed a promising effect on the increased viability of OVX-BMMSC (ANOVA test; LSD test, p = 0.01, p = 0.002). The results of gene expression analysis revealed that the sham- BMMSCs responded optimally to OT treatment. It was also found that OVX-BMMSCs responded optimally to PBMT + OT and PBMT treatments at early and middle stages of osteogenic induction process. Nevertheless, they responded optimally to PBMT + OT and OT especially at the late stage of osteogenic induction process. PBMT and PBMT + OT treatments significantly increased viability of OVX-BMMSC in OIM in vitro. Both PBMT and PBMT + OT treatments could promote mineralization of OVX-BMMSC in the culture medium at early and middle stages of osteogenic induction process. Both OT and PBMT + OT treatments could promote mineralization of OVX-BMMSC in vitro at late stages of osteogenic induction process.

Topics: Animals; Calcification, Physiologic; Cell Differentiation; Cell Survival; Combined Modality Therapy; Female; Low-Level Light Therapy; Mesenchymal Stem Cells; Osteoporosis; Oxytocin; Rats

This study is aimed to determine the efficacy of X-Ray Microtomography (micro-CT) in predicting oxytocin (OT) treatment response in rabbit osteoporosis(OP) model.. Sixty-five rabbits were randomly divided into three groups: control group, ovariectomy (OVX) -vehicle and OVX-oxytocin group. The controls underwent sham surgery. OVX-vehicle and OVX-oxytocin groups were subjected to bilateral OVX. The rabbits in OVX-oxytocin group were injected with oxytocin. In the 0th, 4th, 8th, 10th and 12th weeks post OVX operation, bone mineral density (BMD) and bone micro-architectural parameters were measured in three groups.. Bone mineral density (BMD), bone volume fraction (BV/TV), Trabecular Number (Tb.N), and Trabecular Thickness (Tb.Th) decreased, while Trabecular Spacing (Tb.Sp) and Structure Model Index (SMI) increased overtime in all the three groups. In OVX-oxytocin group, the bone deterioration tendency is slowing down compared with that of the OVX-vehicle group. The BMD of the OVX-oxytocin group was significantly lower than those in the OVX-vehicle group at 12th week (P = 0.017). BV/TV and Tb.Sp in OVX-oxytocin group changed significantly from 8th week (P = 0.043) and 12th week (P = 0.014), which is earlier than that of BMD and other bone micro-architectural parameters.. BV/TV and Tb.Sp changed prior to BMD and other bone micro-architectural parameters with oxytocin intervention, which indicate that they are more sensitive markers for predicting early osteoporosis and treatment monitoring when using micro-CT to evaluate osteoporosis rabbit model.

Topics: Animals; Bone Density; Bone Remodeling; Female; Imaging, Three-Dimensional; Osteoporosis; Ovariectomy; Oxytocin; Rabbits; Random Allocation; X-Ray Microtomography

This study investigated the effects of systemic administration of oxytocin (OT) in osteoporotic rats on implant osseointegration.. Twenty rats were randomly assigned to the control and experimental groups. Initially, the rats underwent bilateral ovariectomy. After 12 weeks, an osteoporosis model was established. Each rat received an implant at the distal and middle femoral metaphysis. Simultaneously, systemic administration was conducted with one group receiving subcutaneous injection of OT (1 mg·kg⁻¹ per day), whereas the other group received placebo injection. After treatment for 4 weeks, another surgery was conducted to remove the thigh bones from the rats containing the implants for an eight-week observation. With the employment of micro-CT, histological observation and push-out test, osseointegration was evaluated. While the rats received thigh-bone removal surgery, another surgery was conducted to remove the tibia metaphysis from the rats of both groups to perform histological observation and micro-CT inspection.. The trabecular bone of tibial samples was intensive and formed woven mesh structure in the experimental group compared with the control group. In the experimental group, the relative bone volume/tissue volume surrounding the implant, the bone contact ratio, and the maximum push-out force of the implant were 0.35%±0.06%, 67.25%±9.06%, and (70.32±10.91) N, respectively, the corresponding values were 0.11%±0.02%, 43.25%±7.01% and (21.65±4.36) N in the control group, and the experimental group increased significantly compared with the control group (P<0.05).. Systemic administration of OT cannot only antagonize the negative effects of osteoporosis but can also promote implant healing and osseointegration of pure titanium implants.. 目的 探讨骨质疏松大鼠全身应用催产素对种植体骨结合的影响。方法 20只大鼠平均分成对照组和实验组，接受双侧卵巢切除术以建立骨质疏松模型。12周后，在每只大鼠的双侧股骨远中干骺端各植入1枚种植体，同时接受催产素全身用药，实验组皮下注射催产素（每天1 mg·kg⁻¹），对照组注射生理盐水。用药4周后，观察8周，手术取出大鼠胫骨和带有种植体的股骨，采用显微CT和组织学染色观察大鼠胫骨的骨质疏松情况，用显微CT、组织学观察和推出试验评价骨结合效果。结果 实验组与对照组相比，胫骨样本的骨小梁增多、密集，交织成网状，骨质疏松模型成功建立。实验组种植体周围的相对骨体积分数为0.35%±0.06%，骨结合率为67.25%±9.06%，最大推出力为（70.32±10.91） N，对照组的相对骨体积分数、骨结合率和最大推出力分别为0.11%±0.02%、43.25%±7.01%、（21.65±4.36） N，实验组较对照组均明显增加（P<0.05）。结论 全身应用催产素可拮抗骨质疏松的负面影响，促进种植体愈合，对纯钛种植体的骨结合具有正向影响。.

Topics: Animals; Dental Implants; Female; Femur; Humans; Osseointegration; Osteoporosis; Ovariectomy; Oxytocin; Prostheses and Implants; Rats; Rats, Sprague-Dawley; Tibia; X-Ray Microtomography

Osteoporosis and overweight/obesity constitute major worldwide public health burdens that are associated with aging. A high proportion of women develop osteoporosis and increased intraabdominal adiposity after menopause. which leads to bone fractures and metabolic disorders. There is no efficient treatment without major side effects for these 2 diseases. We previously showed that the administration of oxytocin (OT) normalizes ovariectomy-induced osteopenia and bone marrow adiposity in mice. Ovariectomized mice, used as an animal model mimicking menopause, were treated with OT or vehicle. Trabecular bone parameters and fat mass were analyzed using micro-computed tomography. Herein, we show that this effect on trabecular bone parameters was mediated through the restoration of osteoblast/osteoclast cross talk via the receptor activator of nuclear factor-κB ligand /osteoprotegerin axis. Moreover, the daily administration of OT normalized body weight and intraabdominal fat depots in ovariectomized mice. Intraabdominal fat mass is more sensitive to OT that sc fat depots, and this inhibitory effect is mediated through inhibition of adipocyte precursor's differentiation with a tendency to lower adipocyte size. OT treatment did not affect food intake, locomotors activity, or energy expenditure, but it did promote a shift in fuel utilization favoring lipid oxidation. In addition, the decrease in fat mass resulted from the inhibition of the adipose precursor's differentiation. Thus, OT constitutes an effective strategy for targeting osteopenia, overweight, and fat mass redistribution without any detrimental effects in a mouse model mimicking the menopause.

Topics: Adipocytes; Adipose Tissue; Animals; Body Weight; Bone Diseases, Metabolic; Cell Culture Techniques; Coculture Techniques; Disease Models, Animal; Female; Leptin; Lipids; Menopause; Mice; Mice, Inbred C57BL; Osteoblasts; Osteoclasts; Osteoporosis; Ovariectomy; Oxygen; Oxytocin; Weight Gain; X-Ray Microtomography

Osteoporosis constitutes a major worldwide public health burden characterized by enhanced skeletal fragility. Bone metabolism is the combination of bone resorption by osteoclasts and bone formation by osteoblasts. Whereas increase in bone resorption is considered as the main contributor of bone loss that may lead to osteoporosis, this loss is accompanied by increased bone marrow adiposity. Osteoblasts and adipocytes share the same precursor cell and an inverse relationship exists between the two lineages. Therefore, identifying signaling pathways that stimulate mesenchymal stem cells osteogenesis at the expense of adipogenesis is of major importance for developing new therapeutic treatments. For this purpose, we identified by transcriptomic analysis the oxytocin receptor pathway as a potential regulator of the osteoblast/adipocyte balance of human multipotent adipose-derived stem (hMADS) cells. Both oxytocin (OT) and carbetocin (a stable OT analogue) negatively modulate adipogenesis while promoting osteogenesis in both hMADS cells and human bone marrow mesenchymal stromal cells. Consistent with these observations, ovariectomized (OVX) mice and rats, which become osteoporotic and exhibit disequilibrium of this balance, have significant decreased OT levels compared to sham-operated controls. Subcutaneous OT injection reverses bone loss in OVX mice and reduces marrow adiposity. Clinically, plasma OT levels are significantly lower in postmenopausal women developing osteoporosis than in their healthy counterparts. Taken together, these results suggest that plasma OT levels represent a novel diagnostic marker for osteoporosis and that OT administration holds promise as a potential therapy for this disease.

Topics: Adipogenesis; Aged; Aged, 80 and over; Animals; Bone Marrow Cells; Cells, Cultured; Child, Preschool; Female; Humans; Male; Mesenchymal Stem Cells; Mice; Middle Aged; Osteoblasts; Osteoclasts; Osteogenesis; Osteoporosis; Osteoporosis, Postmenopausal; Ovariectomy; Oxytocin; Rats; Receptors, Oxytocin

Topics: Humans; Osteoporosis; Oxytocin; Receptors, Oxytocin; RNA, Messenger

A new hypothesis is presented for the first time to explain the etiology of osteoporosis. Prostaglandins (E2 and F2 alpha) at precise concentrations, have been observed to be involved in bone formation. A close association exists between levels of prostaglandins (E2 and F2 alpha) demonstrated in the neonatal mouse leading to bone formation, with estimated prostaglandins (E2 and F2 alpha) concentrations reported in man. Several hormones (vasopressin, oxytocin, luteinizing hormone, follicle-stimulating hormone, cortisol, estradiol, and testosterone) can indirectly affect prostaglandin formation leading to reduced bone formation. The association between these hormones and prostaglandins (E2 and F2 alpha) explains the physiological mechanism whereby estradiol can be effective for the treatment of osteoporosis. This association also explains the etiology of lumbar spondylitis/spondylodynia, reasons for complaints of increased pain in wet cold weather among arthritics and a multitude of other events. Mechanisms related to this interaction between various hormones and the effect of prostaglandins (E2 and F2 alpha) on bone formation are discussed.

Topics: Animals; Bone and Bones; Bone Development; Bone Resorption; Calcitonin; Cholecalciferol; Cortisone; Dinoprost; Dinoprostone; Female; Humans; Menopause; Models, Biological; Osteoporosis; Oxytocin; Parathyroid Hormone; Vasopressins