BACKGROUND: Eucommia ulmoides is a unique monophyletic and tertiary relict in China and is listed as a national second-class precious protected tree species. Eucommia ulmoides, recognized as a traditional Chinese medicine, can tonify the liver and kidneys and strengthen bones and muscles. Modern pharmacological research has proved that Eucommia ulmoides has multiple osteoprotective effects, including prohibiting the occurrence of osteoporosis and arthritis and enhancing the healing of bone fractures and bone defects.
OBJECTIVE: To check its osteotropic effects, which may provide ideas for its potential use for the development of novel drugs to treat osteoporosis, this study evaluated the effect of total flavonoids from Eucommia ulmoides leaves (TFEL) on the acquisition of Peak Bone Mass (PBM) in young female rats.
METHODS: TFEL was isolated, and its purity was confirmed by using a UV spectrophotometer. TFEL with a purity of 85.09% was administered to 6-week-old female rats by oral gavage at a low (50), mid (100), or high (200 mg/kg/d) dose, and the control group was administrated only with the same volume of water. After 13 weeks of treatment, the rats were sacrificed, and serum, different organs, and limb bones (femurs and tibias) were harvested, and the bone turnover markers, organ index, Bone Mineral Density (BMD), biomechanical property, and microstructure parameters were assayed. Furthermore, molecular targets were screened, and network pharmacology analyses were conducted to reveal the potential mechanisms of action of TFEL.
RESULTS: Oral administration of TFEL for 13 weeks decreased the serum level of bone resorption marker TRACP-5b. As revealed by micro-computer tomography analysis, it elevated BMD even at a low dose (50 mg/kg/d) and improved the microstructural parameters, which were also confirmed by H&E histological staining. However, TFEL showed no effects on body weights, organ index, and micromorphology in the uterus. In our network pharmacology study, an intersection analysis screened out 64 shared targets, with quercetin, kaempferol, naringenin, and apigenin regulating the greatest number of targets associated with osteoporosis. Flavonoids in Eucommia ulmoides inhibited the occurrence of osteoporosis potentially through targeting signaling pathways for calcium, VEGF, IL-17, and NF-κB. Furthermore, AKT1, EGFR, PTGS2, VEGFA, and CALM were found to be potentially important target genes for the osteoprotective effects of flavonoids in Eucommia ulmoides.
CONCLUSIONS: The above results suggested that TFEL can be used to elevate the peak bone mass in adolescence in female individuals, which may prevent the occurrence of postmenopausal osteoporosis, and the good safety of TFEL also suggests that it can be used as a food additive for daily life to improve the bone health.

In a Norwegian youth cohort followed from adolescence to young adulthood, bone mineral density (BMD) levels declined at the femoral neck and total hip from 16 to 27 years but continued to increase at the total body indicating a site-specific attainment of peak bone mass.
OBJECTIVE: To examine longitudinal trends in bone mineral density (BMD) levels in Norwegian adolescents into young adulthood.
METHODS: In a prospective cohort design, we followed 980 adolescents (473 (48%) females) aged 16-19 years into adulthood (age of 26-29) on three occasions: 2010-2011 (Fit Futures 1 (FF1)), 2012-2013 (FF2), and 2021-2022 (FF3), measuring BMD (g/cm2) at the femoral neck, total hip, and total body with dual x-ray absorptiometry (DXA). We used linear mixed models to examine longitudinal BMD changes from FF1 to FF3.
RESULTS: From the median age of 16 years (FF1), femoral neck BMD (mean g/cm2 (95% CI)) slightly increased in females from 1.070 (1.059-1.082) to 1.076 (1.065-1.088, p = 0.015) at the median age of 18 years (FF2) but declined to 1.041 (1.029-1.053, p < 0.001) at the median age of 27 years (FF3). Similar patterns were observed in males: 16 years, 1.104 (1.091-1.116); 27 years, 1.063 (1.050-1.077, p < 0.001); and for the total hip in both sexes (both p < 0.001). Total body BMD increased from age 16 to 27 years in both sexes (females: 16 years, 1.141 (1.133-1.148); 27 years, 1.204 (1.196-1.212), p < 0.001; males: 16 years, 1.179 (1.170-1.188); 27 years, 1.310 (1.296-1.315), p < 0.001).
CONCLUSIONS: BMD levels increased from 16 to 18 years at the femoral and total hip sites in young Norwegian females and males, and a small decline was observed at the femoral sites when the participants were followed up to 27 years. Total body BMD continued to increase from adolescence to young adulthood.

Interventional studies offer strong evidence for exercise\'s osteogenic impact on bone particularly during growth. With rising osteoporosis rates in older women, enhancing bone strength early in life is crucial. Thus, investigating the osteogenic effects of different types of physical activities in young females is crucial. Despite varied findings, only two systematic reviews tried to explore this topic without examining how different types of exercise may affect bone health in adolescent girls. The first aim of this systematic review was to assess the impact of exercise training on bone health parameters in adolescent girls, and the second aim was to investigate whether the type of exercise training can modulate this effect. A systematic literature search was conducted using common electronic databases from inception - January 2023. Seven studies (355 participants) were eligible for inclusion in this systematic review. Two studies dealt with resistance training, 3 studies applied plyometric training, 1 study used team sports, and 1 study used dancing. Results indicate that plyometric training increases lumbar spine bone mass in adolescent girls. Well-designed randomized controlled trials with a proper training period (> 12 weeks) are needed to advocate a specific type of training which has the highest osteogenic effect.

Peak bone mass is the amount of bone tissue that is formed when a stable skeletal state is achieved at a young age. To date, there are no established peak bone mass standards nor clear data on the age at which peak bone mass occurs. At the same time, the level of peak bone mass at a young age is an important predictor of the onset of primary osteoporosis. The purpose of this review is to analyze the results of studies of levels of peak bone mass in general, the age of its onset, as well as factors influencing its formation. Factors such as hormonal levels, body composition, physical activity, nutrition, heredity, smoking, lifestyle, prenatal predictors, intestinal microbiota, and vitamin and micronutrient status were considered, and a comprehensive scheme of the influence of these factors on the level of peak bone mass was created. Determining the standards and timing of the formation of peak bone mass, and the factors affecting it, will help in the development of measures to prevent its shortage and the consequent prevention of osteoporosis and concomitant diseases.

OBJECTIVE: To explore and verify the genes related to female peak bone mass(PBM) and osteoporosis (OP) based on bioinformatics.
METHODS: Using GEO data, DNA microarray technology to conduct genome-wide analysis of adult female monocytes with high and low PBM. Cluster analysis, GO enrichment and KEGG analysis were used to analyze the differential genes, and the interaction network of differential genes was further analyzed. OP rat model was established and femur neck tissue staining was performed to further verify the expression of differential genes.
RESULTS: A total of 283 genes were obtained by differential gene screening. Compared with the high PBM samples, 135 genes were up-regulated and 148 genes were down-regulated in the low PBM samples. A total of 7 pathways and 12 differential genes were enriched, and there were differences in the expression of several genes involved in mineral absorption and transport, cellular immunity and other aspects. Among them, voltage-gated Ca2+ channel 1.3(CaV1.3) encoded by CACNA1D gene was significantly enhanced in the femoral neck tissue of OP rat model.
CONCLUSIONS: The above results suggest that the difference in the expression level of CaV1.3 gene may lead to the occurrence of OP in women with low PBM, which provides us with a potential target for the prevention and treatment of OP.

The main aim of the current study was to explore the effects of a 1-year recreational Kung Fu protocol on bone health parameters (bone mineral content (BMC), bone mineral density (BMD), femoral neck geometry and composite indices of femoral neck strength) in a group of healthy inactive young men. 54 young inactive men voluntarily participated in this study, but only 51 of them completed it. The participants were assigned to 2 different groups: control group (n=31) and Kung Fu group (n=20). The Kung Fu group performed two sessions of recreational Kung Fu per week; the duration of each session was 45 minutes. The current study has demonstrated that whole body (WB) BMC, ultra-distal (UD) radius BMD, 1/3 radius BMD, total radius BMD, total forearm BMD, maximal strength, maximum oxygen consumption and jumping performance increased in the Kung Fu group but not in the control group. The percentages of variations in WB BMC, forearm BMD and physical performance parameters were significantly different between the two groups. In conclusion, this study suggests that recreational Kung Fu is an effective method to improve WB BMC, forearm BMD and physical performance parameters in young inactive men.

Weight-bearing exercise (WBE) has been identified as an appropriate approach for increasing peak bone mass, however, there is a lack of specific physical activity recommendations in this area. Thus, the aim of this systematic review is to determine the optimal mode of WBE, specifically identifying the intensity, duration, frequency, and load, to elicit the optimal effect on bone mass in young females, aged 5-18. A literature search was conducted from the 28th of June to the 20th of July 2021 using PubMed/Medline, Web of Science and SPORTDiscus. The search produced 1405 results, of which 15 were deemed appropriate for inclusion. The majority of studies (n=12) found a significant positive effect for at least one bone measure through their respective WBE exposure (p<0.05). Bone mass accrual was found to be site-specific depending on WBE exposure type, load, and maturity status. Also, longitudinal effects on bone mass accrual were found exclusively in gymnastics participants, even if participation level decreased (i.e., retirement). The results of this study support the use of WBE to improve parameters of bone health. However, further research is needed as the optimal mode of WBE to elicit the optimal effect on bone mass is still unclear.

Despite improvements in surgical techniques, current radiotherapy options and development of long-acting somatostatin analogues, biochemical control of acromegaly is not achieved in some patients. The failure to achieve optimal serum growth hormone (RH) and insulin-like growth factor-1 (IGF-1) levels means increased morbidity and mortality of acromegaly patients. The RH receptor antagonist pegvisomant (PEG) is a genetically engineered RH analog that prevents of RH receptor dimerization, i.e. a process that is crucial for the action of RH at the cellular level. The effect of the treatment is suppression of IGF-1 production. In pilot studies, normalization of IGF-1 levels was achieved in up to 90 % of patients receiving PEG. However, PEG efficacy in clinical settings is slightly lower (65 to 97 %) than reported in the key studies. A rare side effect of treatment is elevations of liver transaminases. In addition, pituitary tumor growth progression has been reported in several cases. In this review article, we present long-term data on pegvisomant treatment and discuss its associated risks and benefits.

The effect of calcium supplementation on bone mineral accretion in people under 35 years old is inconclusive. To comprehensively summarize the evidence for the effect of calcium supplementation on bone mineral accretion in young populations (≤35 years).
This is a systematic review and meta-analysis. The Pubmed, Embase, ProQuest, CENTRAL, WHO Global Index Medicus, Clinical Trials.gov, WHO ICTRP, China National Knowledge Infrastructure (CNKI), and Wanfang Data databases were systematically searched from database inception to April 25, 2021. Randomized clinical trials assessing the effects of calcium supplementation on bone mineral density (BMD) or bone mineral content (BMC) in people under 35 years old.
This systematic review and meta-analysis identified 43 studies involving 7,382 subjects. Moderate certainty of evidence showed that calcium supplementation was associated with the accretion of BMD and BMC, especially on femoral neck (standardized mean difference [SMD] 0.627, 95% confidence interval [CI] 0.338-0.915; SMD 0.364, 95% CI 0.134-0.595; respectively) and total body (SMD 0.330, 95% CI 0.163-0.496; SMD 0.149, 95% CI 0.006-0.291), also with a slight improvement effect on lumbar spine BMC (SMD 0.163, 95% CI 0.008-0.317), no effects on total hip BMD and BMC and lumbar spine BMD were observed. Very interestingly, subgroup analyses suggested that the improvement of bone at femoral neck was more pronounced in the peripeak bone mass (PBM) population (20-35 years) than the pre-PBM population (<20 years).
Our findings provided novel insights and evidence in calcium supplementation, which showed that calcium supplementation significantly improves bone mass, implying that preventive calcium supplementation before or around achieving PBM may be a shift in the window of intervention for osteoporosis.
This work was supported by Wenzhou Medical University grant [89219029].
Osteoporosis and bone fractures are common problems among older people, particularly older women. These conditions cause disability and reduce quality of life. Progressive loss of bone mineral density is usually the culprit. So far, strategies to prevent bone weakening with age have produced disappointing results. For example, taking calcium supplements in later life only slightly reduces the risk of osteoporosis or fracture. New approaches are needed. Bone mass increases gradually early in life and peaks and plateaus around 20-35 years of age. After that period, bone mass slowly declines. Some scientists suspect that increasing calcium intake during this period of peak bone mass may reduce osteoporosis or fracture risk later in life. A meta-analysis by Liu, Le et al. shows that boosting calcium intake in young adulthood strengthens bones. The researchers analyzed data from 43 randomized controlled trials that enrolled 7,382 participants. About half the studies looked at the effects of taking calcium supplements and the other half analyzed the effects of a high calcium diet. Boosting calcium intake in people younger than age 35 improved bone mineral density throughout the body. It also increased bone mineral density at the femoral neck, where most hip fractures occur. Calcium supplementation produced larger effects in individuals between the ages of 20 and 35 than in people younger than 20. Both high calcium diets and calcium supplements with doses less than 1000 mg/d boosted bone strength. Higher dose calcium supplements did not provide any extra benefits. The analysis suggests people should pay more attention to bone health during early adulthood. Large randomized clinical trials are needed to confirm the long-term benefits of boosting calcium intake during early adulthood. But if the results are validated, taking calcium supplements, or eating more calcium-rich foods between the ages of 20 and 35 may help individuals build healthier bones and prevent fractures and osteoporosis later in life.

The aim of the current study was to evaluate the effects of different levels of weightlifting training on bone mineral density (BMD) at different body sites (whole body (WB), lumbar spine (LS), femoral neck (FN), upper limbs (UL) and lower limbs (LL)) in a group of adolescents. Three groups of pubertal boys aged 13-15 years were recruited, including a control group (which included 13 untrained adolescents), a moderately trained group (which included 13 non-elite weightlifters, with four sessions of 2 hours per week) and a highly trained group (which included 13 elite weightlifters, with eight sessions of 2 hours per week). The three groups were paired for age and maturation index (using Tanner stages). Body composition, bone mineral content (BMC) and BMD were evaluated by dual-energy X ray absorptiometry (DXA). Physical performance variables (including weightlifting specific exercises, counter movement jump and squat jump) were measured using validated methods. Results showed that the values of BMD and physical performance variables were greater in the group of elite weightlifters compared to the group of non-elite weightlifters and the control group. In addition, the values of BMD and physical performance variables were higher in the group of the non-elite weightlifters compared to those of the control group. After adjusting for lean mass and squat jump, lumbar spine BMD, FN BMD, UL BMD and LL BMD remained significantly higher in the elite weightlifters\' group compared to the two other groups. In conclusion, the current study suggests that elite adolescent weightlifters have greater bone health parameters compared to moderately-trained adolescent weightlifters and untrained adolescents.