Journal of Bone Metabolism

"Bone and bones"

Original Articles

Alcohol Intake and Bone Microarchitecture Deterioration in Older Men: The Prospective Structure of Aging Men’s Bones (STRAMBO) Study: Pawel Szulc, Danielle E. Whittier, Steven K. Boyd, Roland Chapurlat; J Bone Metab 2026;33(3):278-291.
Published online August 31, 2026; DOI: https://doi.org/10.11005/jbm.25.989

Background
Data on the link between alcohol intake and prospectively assessed changes in areal bone mineral density (aBMD) are scarce. Our aim was to assess the association of alcohol intake with bone loss and microarchitectural decline prospectively assessed in older men.
Methods
In 818 men aged 60 to 87 years, bone microarchitecture was assessed at the distal radius and distal tibia (XtremeCT; Scanco Medical). Areal aBMD was assessed by dual energy X-ray absorptiometry (Hologic Inc.). Both were assessed at baseline, then after 4 and 8 years. Linear mixed models were adjusted for age, body mass index, bioavailable 17β-estradiol, osteoprotegerin, parathyroid hormone, Creactive protein and for grip strength (radius) or for the lower limb physical function score (tibia).
Results
At baseline, aBMD and bone microarchitecture measures did not differ across the classes of alcohol intake. During the follow-up, aBMD decrease did not vary differently across the classes of alcohol intake. Men drinking 16 to 112 g alcohol per week had the slowest bone microarchitecture decline (reference group). At the distal radius, trabecular BMD (Tb.BMD) and number (Tb.N) decreased faster in men consuming <16 g/week and in men drinking >224 g/week vs. the reference group. At the distal tibia, cortical thickness (Ct.Th^d), cortical area (Ct.Ar), reaction force, and failure load decreased faster in men consuming <16 g/week and in men drinking >224 g/week versus the reference group.
Conclusions
Moderate alcohol intake is associated with slower bone decline. Very low and higher alcohol intake were associated with faster bone microarchitecture deterioration in older men when assessed prospectively.

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Yerba Mate and Bone Health: Can Antioxidant Capacity Influence Skeletal Outcomes?: Mercedes Lombarte, Laureana Villarreal, Agustina Velázquez, Patricia M. Lupión, Verónica E. Di Loreto, Lucas R. Brun; J Bone Metab 2026;33(3):234-245.
Published online August 31, 2026; DOI: https://doi.org/10.11005/jbm.25.981

Background
Oxidative stress contributes to bone loss, and dietary antioxidants may support skeletal health. This study evaluated the effects of yerba mate (YM) infusion with enhanced antioxidant capacity (AOC; YM+) on skeletal outcomes.
Methods
Female Sprague-Dawley rats (6 weeks old) were randomized into three groups: control (water), YM, and YM+. After 90 days, tibial bone mineral density (BMD), biomechanical strength, histomorphometry, and plasma oxidative stress/antioxidant markers were assessed. Data were analyzed by analysis of variance (p<0.05).
Results
Both YM and YM+ groups showed significantly higher tibial BMD vs. control (YM, +10.1%; YM+, +9.1%; p<0.05). Plasma thiobarbituric acid reactive substances decreased (46% in YM, 55% in YM+), indicating reduced lipid peroxidation. Although YM+ had higher ferric reducing antioxidant power values and total polyphenol content (TPC), skeletal outcomes did not differ between YM and YM+. TPC and alkaline phosphatase (ALP) increased significantly in a dose-dependent manner: TPC (μg/mL gallic acid equivalent): control 456±43.2; YM, 577±45.0; YM+, 634±44.4; ALP (IU/L): 0.201±0.010; 0.265±0.049; 0.321±0.051. Histomorphometry showed no differences in trabecular volume, thickness, number, or separation.
Conclusions
regular YM consumption improved BMD and vertebral mechanical strength. However, increasing AOC did not enhance additional skeletal benefits, indicating that increased AOC did not translate into additional skeletal benefits under the experimental conditions tested. These findings support YM as a potential dietary strategy to promote bone health.

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Differential Effects of Psychogenic Stress on Bone Morphology and Metabolism in Wistar Rats: Sangun Lee, Haruka Tatehana, Takumi Saito, Issei Sugimoto, Yugo Kimura, Ikue Kondo, Atsunori Itagaki; J Bone Metab 2026;33(3):246-258.
Published online August 31, 2026; DOI: https://doi.org/10.11005/jbm.25.977

Background
Psychogenic stress (PS) significantly contributes to the development of various pathological conditions, including psychiatric, cardiovascular, and metabolic disorders. Furthermore, PS has been shown to influence bone health. In this study, we aimed to elucidate PS effects on bone morphology and metabolism during distinct developmental periods in male Wistar rats.
Methods
PS was induced by combined restraint and water immersion stress for 3 hr per day over 4 weeks. In the end of the experiment, femora and tibiae were analyzed to determine bone length, cross-sectional area, and bone mass. Internal organ weights were also recorded. Bone-specific alkaline phosphatase and tartrate-resistant acid phosphatase activities were measured as markers of bone formation and resorption, respectively. Data were analyzed using the Student’s ttest and Scheffé’s multiple comparison test.
Results
PS significantly reduced body and organ weights at all developmental stages, indicating systemic growth suppression. The degree of stress-induced alterations in bone metabolism differed depending on the developmental stage: PS during growth impaired bone formation and enhanced resorption.
Conclusions
Our findings demonstrate that PS exerts stage-specific effects on skeletal development and maintenance. The results highlight the importance of considering developmental stage in evaluating the impact of PS on bone health and suggest potential mechanisms linking chronic stress exposure to altered bone metabolism and increased risk of osteoporosis.

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Comparison of Bone Microarchitecture and Clinical Biomarkers between Diabetic and Non-Diabetic Postmenopausal Osteoporotic Women: Tushar Kumar, Swapnajeet Sahoo, Richa Rattan, Vandana Dhiman, Trupti Nagendra, Raman Saini, Sanjay Kumar Bhadada; J Bone Metab 2026;33(3):292-309.
Published online August 31, 2026; DOI: https://doi.org/10.11005/jbm.25.1011

Background
To characterize skeletal and metabolic profiles in postmenopausal women with osteoporosis, type 2 diabetes mellitus (T2DM), their coexistence (T2DM+osteoporosis), and healthy controls using biochemical markers, dual energy X-ray absorptiometry (DXA), and high-resolution peripheral quantitative computed tomography (HR-pQCT).
Methods
This cross-sectional study included 220 postmenopausal women (60 each in osteoporosis, T2DM, and T2DM+osteoporosis groups; 40 controls). Participants underwent biochemical, endocrine, and hematological profiling, DXA of the spine and hip, and HR-pQCT imaging at the distal radius and tibia. Bone turnover markers (propeptide of type I collagen, C-terminal telopeptide), parathyroid hormone, and 25-hydroxy-vitamin D were assessed. Data were analyzed using analysis of variance and correlation analyses.
Results
The osteoporosis and T2DM+osteoporosis groups demonstrated significantly lower areal bone mineral density (BMD), elevated bone turnover markers, and marked deterioration in cortical and trabecular microarchitecture. In contrast, T2DM participants exhibited preserved or higher BMD but showed microarchitectural alterations on HR-pQCT. Significant inverse correlations between DXA and HR-pQCT parameters were observed in osteoporosis and T2DM+osteoporosis groups, whereas such associations were not evident in T2DM.
Conclusions
Distinct skeletal phenotypes were observed across osteoporosis, T2DM, and T2DM+osteoporosis. HR-pQCT identified structural deficits not captured by DXA, highlighting that microarchitectural assessment may provide additional insights beyond areal BMD; however, these findings are associative and hypothesis-generating.

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Review Article

Polypharmacy and Bone Health in Patients with Type 2 Diabetes Mellitus: A Narrative Review: Israa O. Kashmoola, Shatha H. Mohammad, Mohammad H. Alsaaty; J Bone Metab 2026;33(2):127-140.
Published online May 31, 2026; DOI: https://doi.org/10.11005/jbm.25.975

Patients with type 2 diabetes mellitus (T2DM) commonly demonstrate reduced bone quality and elevated fracture risk rates despite having normal or elevated bone mineral density (BMD). Beyond the pathophysiological effect of diabetes, polypharmacy has emerged as a potential, yet underappreciated contributor of skeletal fragility. To explore this association, a thorough search of the literature was conducted using PubMed, Google Scholar, and Web of Science. and Scopus for articles published in English language until October 2025. Studies addressing diabetes, polypharmacy, bone health, and drug-related skeletal outcomes were identified and included. A divergent effect on bone health was evident in patients using antidiabetic agents, with thiazolidinediones, sulfonylurea and some insulin regimens increase fracture risk. Whereas metformin, incretinbased therapies and sodium-glucose co-transporter 2 inhibitors appear neutral or protective. Concerning non-antidiabetic medication used in T2DM, glucocorticoids, selective serotonin reuptake inhibitors, proton pump inhibitors and loop diuretics are among the drugs that worsen the bone architecture, causing increased fracture risk. On the other hand, statins, β-blockers, angiotensin converting enzyme inhibitors, thiazide diuretics and angiotensin receptor antagonists are bone protective. Such cumulative impact of polypharmacy involves drug-drug interactions, increased fall potential, and attenuation of antiresorptive therapy. Clinical interventions to prevent skeletal deterioration include periodic medications review, deprescribing of high-risk agents, calcium and vitamin D supplementation, and life-style modifications. Personalized and multidisciplinary strategies are essential to balance metabolic status with long-term skeletal preservation in patients with T2DM exposed to polypharmacy.

Citations

Citations to this article as recorded by

1. Type 2 Diabetes and Falls Incidents among the Elderly: An Umbrella Review of their Associations with Vitamin D Levels and Other Salient Peer Reviewed Research Observations
Ray Marks
Journal of Orthopaedic Science and Research.2026; 7(3): 1. CrossRef

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Original Article

Biomimetic Architectural Cover Accelerates Osseointegration of Titanium Implants: Su-Jin Kim, Eun Chae Kim, Weon-Young Choi, Seung-Jae Lee, Je-Hwang Ryu; J Bone Metab 2026;33(1):30-39.
Published online February 28, 2026; DOI: https://doi.org/10.11005/jbm.26.1003

Background
Although various surface modifications enhance titanium (Ti) implant osseointegration, achieving rapid bone formation comparable to native healing remains challenging. Current strategies primarily focus on micro-scale topography, often overlooking the critical role of macroscopic three-dimensional (3D) architecture in osteoconduction.
Methods
We hypothesized that mimicking native bone’s porous architecture is key to accelerating osseointegration. First, we verified the impact of structural continuity by comparing standard Ti implants with decellularized bone grafts in a mouse calvaria defect model. Subsequently, we developed a biomimetic polycaprolactone (PCL)-based 3D architectural cover (Cover-type) and evaluated its osseointegration efficacy in a rat femur model against conventional Ti implants.
Results
The mouse study confirmed that decellularized bone integrated significantly faster than Ti, highlighting the necessity of 3D continuity. In the rat model, micro-computed tomography analysis indicated a clear trend of increased bone formation in the Cover-type group, though statistical significance was limited by sample size. However, histological analysis confirmed a statistically significant enhancement in bone-to-implant contact compared to controls (P<0.05). The PCL structure served as a scaffold for cell migration, effectively bridging the implant-bone gap.
Conclusions
These findings suggest that providing a bone-like 3D environment via a PCL cover may enhance histological osseointegration, rather than relying solely on surface chemistry.

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Review Article

Endocrine Regulation of Osteoporosis: Insights from the Brain-Bone Axis Theory: Xin Chen, Jialing Wang, Tingting Deng, Qing Ni, Fanjie Liu; J Bone Metab 2025;32(4):247-262.
Published online November 30, 2025; DOI: https://doi.org/10.11005/jbm.25.887

Osteoporosis (OP) is a systemic skeletal disease characterized by reduced bone mass and increased risk of fractures, with limitations in traditional treatment methods. The “brainbone axis” theory has revealed a bidirectional regulatory network between the central nervous system and the skeletal system, providing new insights into the mechanisms and treatment of OP. This review summarizes the bidirectional regulatory mechanisms of the “brain-bone axis”, including descending pathways (such as the regulation of bone metabolism by the sympathetic nervous system, parasympathetic nervous system, and hypothalamic nuclei) and ascending feedback (such as bone-derived factors influencing central nervous system function through the blood-brain barrier), and explores the synergistic roles of endocrine systems (such as the thyroid axis and gonadal axis) within this network. Additionally, the article summarizes multi-modal treatment strategies based on the “brain-bone axis” theory, offering new insights for the precise prevention and treatment of OP. Future research should further integrate basic and clinical studies to advance the paradigm shift of OP from a localized bone disorder to a systemic disease.

Citations

Citations to this article as recorded by

1. Poor Bone Health Associated with Reduced Cerebral Perfusion and Brain Volume in Older Adults
Tiffany Y. So, James F. Griffith, Jill Abrigo, Lin Shi, David K. W. Yeung, Jason Leung, Timothy Kwok, Vincent C. T. Mok
Diagnostics.2026; 16(4): 529. CrossRef
2. A bibliometric analysis of the associations between Osteoporosis and Central Nervous System
Guangbin Yu, YingYing Gao, Hongyuan Song, Xiong Chen, Sitong Kuang, Conghan Su, le Li, Manguang Liang, Guocai Chen
Experimental Gerontology.2026; 220: 113175. CrossRef
3. The recent progression of extracellular vesicles application in osteoporosis
Rui Liu, Wenyu Li, Junzheng Yang
Frontiers in Pharmacology.2026;[Epub] CrossRef
4. Reframing Osteoblast Homeostasis as a Systemic Endocrine–Metabolic Node: Mechanisms, Inter‐Organ Crosstalk, and Translational Strategies
Yang Li, Zheng Chen, Guangchen Li, Shiwei Ji, Ruofang Yin, Shizhuo Wang
Comprehensive Physiology.2026;[Epub] CrossRef
5. RANKL-containing exosome-mediated bone-brain axis: a molecular hypothesis for post-fracture Dementia
Quanzhou Lv, Siqi Huang, Yuqi Ren, Shuyu Fan, Xinyu Yuan, Yan Li
Medical Hypotheses.2026; 216: 112128. CrossRef

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Original Articles

Side-to-Side Differences in Bone Mineral Density, Bone Mineral Content, and Lean Mass in Healthy Subjects: María Lorena Brance, Silvana Di Gregorio, Luis A. Ramírez Stieben, Luis Miguel Del Río Barquero, Lucas R. Brun; J Bone Metab 2025;32(3):212-220.
Published online August 31, 2025; DOI: https://doi.org/10.11005/jbm.25.865

Background
Limb dominance is influenced by daily activity and muscle strength. Previous studies have demonstrated lateral differences in bone mineral density (BMD), bone mineral content (BMC), and lean mass as a result of asymmetric mechanical loading. Understanding these variations is crucial, especially in conditions with regional bone demineralization, where the contralateral limb can serve as a reference. We aimed to analyze side-to-side differences in BMD, BMC, and lean mass, as measured by dual energy X-ray absorptiometry (DXA), in healthy subjects.
Methods
A cross-sectional study included 802 whole-body composition assessments in Spanish adults (20-80 years). Athletes and individuals with bone metabolism disorders were excluded. Hand and foot dominance were self-reported. BMD, BMC, and lean mass were measured using a DXA scanner (Lunar Prodigy).
Results
The sample (57.1% women, 42.9% men; mean age, 53.0±16.7 years) showed strong correlations between dominant and non-dominant limbs (r>0.90). The dominant upper limb had significantly higher BMD (~4%), BMC (~5-6%), and lean mass (~3-4%) in both sexes. In women, the dominant lower limb showed slight differences (~1%), while in men, only lean mass was significantly higher. Aging led to BMD and BMC reductions after a peak in the fourth decade in women and the third in men. Lean mass showed a higher decline in men in both upper and lower limbs.
Conclusions
Limb dominance affects body composition differently between sexes, primarily in the upper limb, potentially due to differences in physical activity or mechanical loading. This study provides insight into how laterality and aging influence body composition in healthy individuals.

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Identification of Bone Metastasis-Related Gene Networks in Lung Cancer: Implications for Bone Metabolism: Jungwoo Kim, Seong-Ho Park, Junho K. Hur, Sung Bae Park; J Bone Metab 2025;32(3):232-243.
Published online August 31, 2025; DOI: https://doi.org/10.11005/jbm.25.863

Background
This study aimed to infer a causal gene network associated with bone metastasis in lung cancer and to validate its reliability through experimental gene expression analysis.
Methods
Using DNA microarray data from the Gene Expression Omnibus, we analyzed samples from primary lung cancer and those with bone metastasis. Commonly expressed genes in both groups were identified, and a causal network was inferred using Bayesian network inference with Java Objects based on the Bayesian Dirichlet score. To evaluate the network, we predicted the expression changes of downstream genes following knockdown of a key upstream gene and compared these predictions with mRNA expression levels in fatty acid desaturase 1 (FADS1)-knockdown lung cancer cells.
Results
The genes FADS1, cardiotrophin-like cytokine factor 1 (CLCF1), chromosome 4 open reading frame 48, sushi, nidogen and EGF like domains 1, FK506-binding protein 15, and coenzyme Q10A (COQ10A) were identified as directly associated with lung cancer bone metastasis. Among them, FADS1 appeared to have a regulatory role, influencing downstream targets. Notably, CLCF1 and COQ10A showed significantly increased expression in FADS1-knockdown cells, consistent with the network’s predictions.
Conclusions
These findings suggest that Bayesian network analysis is a reliable machine learning approach for uncovering causal gene relationships in cancer metastasis. Furthermore, FADS1 may serve as a potential therapeutic target in lung cancer bone metastasis. The validity of this network was supported by in vitro experiments using a lung cancer cell line.

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Positive Effect of Yerba Mate (Ilex paraguariensis) Consumption on Bone Mineral Density in Postmenopausal Women Assessed by Dual Energy X-Ray Absorptiometry-Based 3-Dimensional Modeling: Lucas R. Brun, Muriel M. Henríquez, Luis A. Ramírez Stieben, Mariana Cusumano, Jorge Homero Wilches-Visbal, Fernando Daniel Saraví, María Lorena Brance; J Bone Metab 2025;32(2):123-132.
Published online May 31, 2025; DOI: https://doi.org/10.11005/jbm.24.827

Background
Yerba mate (YM) drinking is associated with higher lumbar spine and femoral neck bone mineral density (BMD) in postmenopausal women. We analyzed its effect on total hip BMD and reported the contribution of the trabecular and cortical components to this effect.
Methods
A control group of 147 non-drinkers was compared to 153 YM drinkers. Left hip BMD was measured using dual energy X-ray absorptiometry (DXA), and three-dimensional (3D)-Shaper software was used to estimate integral volumetric BMD (vBMD), cortical surface BMD (sBMD), and trabecular vBMD through 3D modeling.
Results
No significant difference was found between groups in either age (p=0.746) or body mass index (BMI; p=0.329). The YM group had significantly higher total hip BMD, integral vBMD, cortical sBMD, and trabecular BMD (all p<0.0001). The frequency of DXA-based osteoporosis diagnosis was lower in YM drinkers (3.3% vs. 10.9%; odds ratio [OR], 0.276). The rate of low-impact fractures was significantly reduced in YM drinkers (5.9% vs. 12.9%; OR, 2.197). Linear regression analyses revealed that cortical and trabecular parameters correlated positively with BMI and negatively with age in both groups. The slope of the lines did not differ between groups, but the elevation was uniformly higher in the YM group (p=0.0004 to p<0.0001).
Conclusions
Our study provides novel insights into YM consumption and bone health in postmenopausal women. We confirm its positive association with BMD and demonstrate, for the first time, that both cortical and trabecular compartments contribute to this effect. Our findings also suggest a potential protective role of YM against osteoporosis and fragility fractures.

Citations

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1. Effect of Caffeine on the Skeletal System—A Review of Experimental Studies
Paulina Stańczak, Wiktor Krzysztofik, Wiktoria Rudolf, Kacper Grzywnowicz, Joanna Folwarczna
Nutrients.2026; 18(13): 2089. CrossRef
2. Independent Associations of Appendicular Skeletal Muscle Mass Index and Waist Circumference with Site-Specific Bone Mineral Density in Postmenopausal Women: A Real-World Cross-Sectional Study
Pattama Tongdee, Sajeera Kupittayanant, Khanidtha Marungrueng, Sayah Ongsricharoenbhorn, Porntip Nimkuntod
Healthcare.2026; 14(16): 2663. CrossRef
3. Yerba Mate and Bone Health: Can Antioxidant Capacity Influence Skeletal Outcomes?
Mercedes Lombarte, Laureana Villarreal, Agustina Velázquez, Patricia M. Lupión, Verónica E. Di Loreto, Lucas R. Brun
Journal of Bone Metabolism.2026; 33(3): 234. CrossRef
4. Yerba Mate (Ilex paraguariensis) and Rheumatoid Arthritis: A Systematic Review of Mechanistic and Clinical Evidence
Manuela Cassotta, Qingwei Cao, Haixia Hu, Carlos Rabeiro Martinez, Luis Alonso Dzul Lopez, Santos Gracia Villar, Maurizio Battino, Francesca Giampieri
Nutrients.2025; 17(24): 3853. CrossRef

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Age- and Sex-Related Volumetric Density Differences in Trabecular and Cortical Bone of the Proximal Femur in Healthy Population: María Lorena Brance, Fernando Daniel Saraví, Muriel M. Henríquez, María Silvia Larroudé, Jorge E. Jacobo, Sebastian Abalo Araujo, Vanesa Longobardi, María Bélen Zanchetta, María Rosa Ulla, Florencia Martos, Helena Salerni, Beatriz Oliveri, Marina Soledad Bonanno, Naraline Luna Meneses, Pilar Diaz Baclini, Luis A. Ramírez Stieben, Silvana Di Gregorio, Lucas R. Brun; J Bone Metab 2024;31(4):279-289.
Published online November 30, 2024; DOI: https://doi.org/10.11005/jbm.24.765

Background
There are age- and sex-related increases in the prevalence of osteoporosis. Bone densitometry based on dual energy X-ray absorptiometry (DXA) is the gold standard for the assessment of bone mineral density (BMD). Three-dimensional (3D) analysis of the proximal femur (3D-DXA) allows discrimination between cortical and trabecular compartments, and it has shown a good correlation with computed tomography. We aimed to assess age- and sex-related volumetric density differences in trabecular and cortical bone using 3D-DXA and determine the reference intervals for integral volumetric (v)BMD within the Argentine population.
Methods
Healthy female and male adult subjects (N=1,354) from Argentina were included. Hip BMD was measured using DXA, and 3D analysis was performed using 3D-Shaper software. The integral vBMD, cortical surface BMD, and trabecular vBMD (trab vBMD) were measured.
Results
The study population included 73.9% women (N=1,001) and 26.13% men (N=353). We found a significant decrease in integral vBMD between 20 and 90 years in both sexes (women, -23.1%; men, -16.6%). Bone loss indicated in the integral vBMD results was mainly due to a decrease in trabecular bone in both sexes (women, -33.4%; men, -27.7%). The age-related loss of cortical bone density was less and was limited to the female population, without no age-related differences in men. Moreover, 3D-DXA allowed us to propose reference intervals for integral vBMD.
Conclusions
We found age- and sex-related bone loss between 20 and 90 years in an Argentine cohort via integral vBMD measurements using 3D-DXA, mainly due to decreases in trabecular bone in both sexes. The age-related loss of cortical bone density was less and was limited to the female population.

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Griselda-Adriana Cruz-Priego, Miguel Ángel Guagnelli, Sergio Ortiz Santiago, Karina Geraldine González Castelan, Rita A. Gomez-Diaz, Ludovic Humbert, Patricia Clark
Archives of Medical Research.2026; 57(1): 103269. CrossRef
2. Investigating the association between creatinine-adjusted urinary catecholamines and site-specific bone mineral density in older adults
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Hormone Molecular Biology and Clinical Investigation.2026; 47(1): 9. CrossRef
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Environmental Pollution.2026; 396: 127884. CrossRef
4. Differences in lumbar spine bone mineral density measured by quantitative computed tomography and dual-energy X-ray absorptiometry: an age- and sex-specific analysis
Xingjian Li, Chunchao Huang, Xiaoqian Wang, Wencong Chen, Yi Peng, Junjie Yuan, Wentao Lin, Yawei Liu
Journal of Orthopaedic Surgery and Research.2026;[Epub] CrossRef
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Journal of Health Sciences and Medicine.2026; 9(4): 1010. CrossRef
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7. Positive Effect of Yerba Mate (Ilex paraguariensis) Consumption on Bone Mineral Density in Postmenopausal Women Assessed by Dual Energy X-Ray Absorptiometry-Based 3-Dimensional Modeling
Lucas R. Brun, Muriel M. Henríquez, Luis A. Ramírez Stieben, Mariana Cusumano, Jorge Homero Wilches-Visbal, Fernando Daniel Saraví, María Lorena Brance
Journal of Bone Metabolism.2025; 32(2): 123. CrossRef
8. Side-to-Side Differences in Bone Mineral Density, Bone Mineral Content, and Lean Mass in Healthy Subjects
María Lorena Brance, Silvana Di Gregorio, Luis A. Ramírez Stieben, Luis Miguel Del Río Barquero, Lucas R. Brun
Journal of Bone Metabolism.2025; 32(3): 212. CrossRef
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11. Determinants of Bone Mineral Density in Postmenopausal Women: The Role of Lean and Fat Mass by Dual Energy X-Ray Absorptiometry Assessment
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Journal of Bone Metabolism.2025; 32(4): 306. CrossRef

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Review Article

Exploring the Interplay between Vitamin D, Insulin Resistance, Obesity and Skeletal Health: Mohammed N. Abed, Fawaz A. Alassaf, Mohannad E. Qazzaz; J Bone Metab 2024;31(2):75-89.
Published online May 31, 2024; DOI: https://doi.org/10.11005/jbm.2024.31.2.75

Vitamin D (ViD), plays an important role in calcium absorption and bone mineralization, is associated with bone mineral density. Severe deficiency in ViD has long been linked to conditions such as rickets in children and osteomalacia in adults, revealing its substantial role in skeletal health. Additionally, investigations show an existing interconnection between ViD and insulin resistance (Ins-R), especially in patients with type 2 diabetes mellitus (T2DM). Obesity, in conjunction with Ins-R, may augment the risk of osteoporosis and deterioration of skeletal health. This review aims to examine recent studies on the interplay between ViD, Ins-R, obesity, and their impact on skeletal health, to offer insights into potential therapeutic strategies. Cochrane Library, Google Scholar, and Pubmed were searched to investigate relevant studies until December 2023. Current research demonstrates ViD’s impact on pancreatic β-cell function, systemic inflammation, and insulin action regulation. Our findings highlight an intricate association between ViD, Ins-R, obesity, and skeletal health, providing a perspective for the prevention and/or treatment of skeletal disorders in patients with obesity, Ins-R, and T2DM.

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Journal of Health and Allied Sciences NU.2026; 16: 411. CrossRef
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Advances in Clinical Medicine.2026; 16(07): 804. CrossRef
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Jundishapur Journal of Natural Pharmaceutical Products.2025;[Epub] CrossRef
5. Positive Effect of Yerba Mate (Ilex paraguariensis) Consumption on Bone Mineral Density in Postmenopausal Women Assessed by Dual Energy X-Ray Absorptiometry-Based 3-Dimensional Modeling
Lucas R. Brun, Muriel M. Henríquez, Luis A. Ramírez Stieben, Mariana Cusumano, Jorge Homero Wilches-Visbal, Fernando Daniel Saraví, María Lorena Brance
Journal of Bone Metabolism.2025; 32(2): 123. CrossRef
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International Journal of Environmental Research and Public Health.2025; 22(6): 949. CrossRef
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Original Article

Melatonin Protects Bone Microarchitecture against Deterioration due to High-Fat Diet-Induced Obesity: Bukyung Kim, Yeon Ji Kim, Jae Hyun Kim, Kwangkuk Park, Hyungjune Ku, Young-Sik Choi; J Bone Metab 2023;30(1):69-75.
Published online February 28, 2023; DOI: https://doi.org/10.11005/jbm.2023.30.1.69

Background
We evaluated the protective effects of melatonin against high-fat diet (HFD)-induced deterioration of bone microarchitecture using high-resolution peripheral quantitative computed tomography (HR-pQCT).
Methods
Four-week-old male C57BL/6 mice were divided into control (chow diet group), HFD, and HFD + melatonin-administered groups. Mice were sacrificed after 14 weeks, and the right femur was extracted. The microskeletal structure of the femur was analyzed using SkyScan1173 (version 1.6). A 3-dimensional image was reconstructed using the Nrecon (version 1.7.0.4) program.
Results
Bone volume (BV) was significantly increased in the HFD group compared with that in the normal diet group, and that of the melatonin group also increased significantly compared with BV of the normal diet group (p<0.05). Percent BV/total volume [TV] and bone surface/BV were significantly higher in both the HFD and melatonin groups than in the normal diet group (p<0.05), and the melatonin group had the highest BV/total volume (TV). BMD was lower in the HFD than in the normal diet group and was the highest in the melatonin group.
Conclusions
This study shows that melatonin inhibited the deterioration of microarchitecture induced by a HFD. A better understanding of the protective effect of melatonin on bone microarchitecture and mechanisms could provide fracture prevention for people who are obese.

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Review Articles

Molecular and Cellular Crosstalk between Bone and Brain: Accessing Bidirectional Neural and Musculoskeletal Signaling during Aging and Disease: Charles A. Schurman, Jordan B. Burton, Jacob Rose, Lisa M. Ellerby, Tamara Alliston, Birgit Schilling; J Bone Metab 2023;30(1):1-29.
Published online February 28, 2023; DOI: https://doi.org/10.11005/jbm.2023.30.1.1

Molecular omics technologies, including proteomics, have enabled the elucidation of key signaling pathways that mediate bidirectional communication between the brain and bone tissues. Here we provide a brief summary of the clinical and molecular evidence of the need to study the bone–brain axis of cross-tissue cellular communication. Clear clinical and molecular evidence suggests biological interactions and similarities between bone and brain cells. Here we review the current mass spectrometric techniques for studying brain and bone diseases with an emphasis on neurodegenerative diseases and osteoarthritis/osteoporosis, respectively. Further study of the bone–brain axis on a molecular level and evaluation of the role of proteins, neuropeptides, osteokines, and hormones in molecular pathways linked to bone and brain diseases is critically needed. The use of mass spectrometry and other omics technologies to analyze these cross-tissue signaling events and interactions will help us better understand disease progression and comorbidities and potentially identify new pathways and targets for therapeutic interventions. Proteomic measurements are particularly favorable for investigating the role of signaling and secreted and circulating analytes and identifying molecular and metabolic pathways implicated in age-related diseases.

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The Extracellular Signal-Regulated Kinase Mitogen-Activated Protein Kinase Pathway in Osteoblasts: Matthew B. Greenblatt, Jae-Hyuck Shim, Seoyeon Bok, Jung-Min Kim; J Bone Metab 2022;29(1):1-15.
Published online February 28, 2022; DOI: https://doi.org/10.11005/jbm.2022.29.1.1

Extracellular signal-regulated kinases (ERKs) are evolutionarily ancient signal transducers of the mitogen-activated protein kinase (MAPK) family that have long been linked to the regulation of osteoblast differentiation and bone formation. Here, we review the physiological functions, biochemistry, upstream activators, and downstream substrates of the ERK pathway. ERK is activated in skeletal progenitors and regulates osteoblast differentiation and skeletal mineralization, with ERK serving as a key regulator of Runt-related transcription factor 2, a critical transcription factor for osteoblast differentiation. However, new evidence highlights context-dependent changes in ERK MAPK pathway wiring and function, indicating a broader set of physiological roles associated with changes in ERK pathway components or substrates. Consistent with this importance, several human skeletal dysplasias are associated with dysregulation of the ERK MAPK pathway, including neurofibromatosis type 1 and Noonan syndrome. The continually broadening array of drugs targeting the ERK pathway for the treatment of cancer and other disorders makes it increasingly important to understand how interference with this pathway impacts bone metabolism, highlighting the importance of mouse studies to model the role of the ERK MAPK pathway in bone formation.

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The Potential Role of Exercise Training and Mechanical Loading on Bone-Associated Skeletal Nerves: Stefano Negri, T. Jake Samuel, Seungyong Lee; J Bone Metab 2021;28(4):267-277.
Published online November 30, 2021; DOI: https://doi.org/10.11005/jbm.2021.28.4.267

The spatial distribution, innervation, and functional role of the bone-associated skeletal nerves have been previously reported in detail. However, studies examining exercise-induced associations between skeletal nerves and bone metabolism are limited. This review introduces a potential relationship between exercise and the skeletal nerves and discusses how it can contribute to exercise-induced bone anabolism. First, the background and current understanding of nerve fiber types and their functions in the skeleton are provided. Next, the influence of exercise and mechanical loading on the skeletal nervous system is elaborated. Effective synthesis of recent studies could serve as an established baseline for the novel discovery of the effects of exercise on skeletal nerve density and bone anabolic activity in the future. Therefore, this review overviews the existing evidence for the neural control of bone metabolism and the potential positive effects of exercise on the peripheral skeletal nervous system. The influence of exercise training models on the relationships of sensory nerve signals with osteoblast-mediated bone formation and the increased bone volume provides the first insight on the potential importance of exercise training in stimulating positive adaptations in the skeletal nerve-bone interaction and its downstream effect on bone metabolism, thereby highlighting its therapeutic potential in a variety of clinical populations.

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Original Article

Physical Activity and Bone Health in Men: A Systematic Review and Meta-Analysis: Maureen C. Ashe, Isis Kelly dos Santos, Nicola Y. Edward, Laura A. Burnett, Rosanne Barnes, Lena Fleig, Joseph H. Puyat, Joanna E. M. Sale, Heather A. McKay, Lora M Giangregorio; J Bone Metab 2021;28(1):27-39.
Published online February 28, 2021; DOI: https://doi.org/10.11005/jbm.2021.28.1.27

Background
Research on osteoporosis and physical activity often focuses on women. We aimed to conduct a systematic review to assess the benefits and harms of physical activity interventions for men’s bone health.
Methods
We used standard methods and searched for randomized controlled trials (RCTs) (duration, ≥6 months) published in all languages across multiple databases and trial registries. The last search was conducted on July 22, 2020.
Results
We included 11 studies (14 publications), resulting in a sample of N=723 men (range, 17–132 participants). We found low-certainty evidence that physical activity has little influence on the areal bone mineral density (aBMD) at the total hip (5 RCTs, N=324; mean difference [MD], 0.03 [95 confidence interval (CI), 0.01 to 0.05]) and little or no influence on the aBMD at the femoral neck (3 RCTs, N=186; MD, 0.00 [95% CI, -0.04 to 0.04]), lumbar spine (3 RCTs; N=213; MD, 0.05 [95% CI, -0.01 to 0.11]), and whole body (4 RCTs, N=203; MD, -0.00 [95% CI, -0.03 to 0.02]).
Conclusions
We found low-certainty evidence that physical activity (≥6 months) has some effect on the total hip in men, but new evidence may change this finding. This review highlights the gap in the evidence on specific intervention prescriptions that can benefit the bone geometry, structure, microarchitecture, and, ultimately, bone strength in men. Future research should engage in comprehensive reporting of harms, quality of life outcomes, advanced imaging findings, and long-term interventions.

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Review Article

Comparison and Contrast of Bone and Dentin in Genetic Disorder, Morphology and Regeneration: A Review: Jaehyun Kim, Gayeong Lee, Woo Sung Chang, Si hyoung Ki, Joo-Cheol Park; J Bone Metab 2021;28(1):1-10.
Published online February 28, 2021; DOI: https://doi.org/10.11005/jbm.2021.28.1.1

The bone and dentin have distinct healing processes. The healing process of bones is regenerative, as newly formed tissues are morphologically and functionally similar to the original bone structures. In contrast, the healing process of dentin is reparative due to its failure to replicate some of its key morphological features. In this review, we compare and contrast the healing processes of bone and dentin. We describe how distinct morphological and physiological structures of the 2 tissues translate into different signaling molecules, growth factors, and matrix protein secretion.

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Original Articles

Impact of Artistic Gymnastics on Bone Formation Marker, Density and Geometry in Female Adolescents: ABCD-Growth Study: Isabella Neto Exupério, Ricardo Ribeiro Agostinete, André Oliveira Werneck, Santiago Maillane-Vanegas, Rafael Luiz-de-Marco, Eduardo D.L. Mesquita, Han C.G. Kemper, Rômulo Araújo Fernandes; J Bone Metab 2019;26(2):75-82.
Published online May 31, 2019; DOI: https://doi.org/10.11005/jbm.2019.26.2.75

Background

To compare bone density accrual and markers of bone geometry and formation between female adolescents engaged and not engaged in artistic gymnastics (AGs).

Methods

This was a 12-month longitudinal study involving 20 female adolescents, including 10 controls and 10 gymnasts (AGs) aged 11 to 16 years. At baseline, the gymnasts had a minimum of 12 months of practice, and the controls reported no participation in any organized sport. Bone mineral density (BMD) was measured in the lower limbs, upper limbs, spine, and whole body. In addition, BMD and geometrical properties of the femur were assessed. As a bone formation marker, osteocalcin level was measured.

Results

Femoral aspects were increased in the gymnasts by 19% (P=0.009), 14% (P=0.047), and 10% (P=0.046) in the Ward's triangle, trochanter, and the overall bone, respectively, than in the control girls. Geometrical parameters, bone accrual, and osteocalcin levels were similar in both groups. The weekly training load explained 30.8% of all bone gains on the lower limbs and affected the density on parts of the femur.

Conclusions

The gymnasts, after a 12-month follow-up, demonstrated a higher BMD in the Ward's triangle and whole femur than the controls, as well as an improvement in femur density. These changes were mainly due to the weekly training load. Lastly, the gymnasts had significant bone accrual (after 12 months) in the upper limbs, lower limbs, and whole body.

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1. Bone Health in Former Artistic Gymnasts Aged 45 Years and Over: Case–Control Comparison with Controls and Reference Populations
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Track and Field Practice and Bone Outcomes among Adolescents: A Pilot Study (ABCD-Growth Study): Yuri da Silva Ventura Faustino-da-Silva, Ricardo Ribeiro Agostinete, André Oliveira Werneck, Santiago Maillane-Vanegas, Kyle Robinson Lynch, Isabella Neto Exupério, Igor Hideki Ito, Romulo Araújo Fernandes; J Bone Metab 2018;25(1):35-42.
Published online February 28, 2018; DOI: https://doi.org/10.11005/jbm.2018.25.1.35

Background

Osteoporosis is considered a public health problem with high worldwide prevalence. One approach to prevention is through the promotion of physical activity, especially exercise, during adolescence.

Methods

This study compared bone variables in different body segments in adolescents according to participation in track and field. The study included 34 adolescents (22 boys), of whom 17 were track and field athletes and 17 were control subjects. Bone mineral density (BMD, g/cm²) and bone mineral content (BMC, g) were analyzed using dual energy X-ray absorptiometry (total body stratified by body segments). Peak height velocity was used to estimate somatic maturation.

Results

Athletes had higher BMD (P=0.003) and BMC (P=0.011) values in the lower limbs and higher whole body BMD (P=0.025) than the control group. However, when adjusted for confounding factors, the difference was not maintained. The groups had similar lean soft tissue values (P=0.094). Training overload was positively correlated with BMD in the upper limbs (r=0.504; 95% confidence interval, 0.031-0.793). Although track and field athletes had higher BMD and BMC values in the lower limbs, these differences were not significant when adjusted for confounding factors.

Conclusions

Track and field participation in adolescence appears to influence BMD and BMC in lower limbs, and fat-free mass seems to mediate this effect. Also, higher training loads were found to be positive for bone health in upper limbs.

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Journal of Sports Sciences.2020; 38(24): 2811. CrossRef
4. Impact of Artistic Gymnastics on Bone Formation Marker, Density and Geometry in Female Adolescents: ABCD-Growth Study
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Review Articles

Bone Biology and Anabolic Therapies for Bone: Current Status and Future Prospects: T. John Martin; J Bone Metab 2014;21(1):8-20.
Published online February 28, 2014; DOI: https://doi.org/10.11005/jbm.2014.21.1.8

Bone is continuously remodelled at many sites asynchronously throughout the skeleton, with bone formation and resorption balanced at these sites to retain bone structure. Negative balance resulting in bone loss and osteoporosis, with consequent fractures, has mainly been prevented or treated by anti-resorptive drugs that inhibit osteoclast formation and/or activity, with new prospects now of anabolic treatments that restore bone that has been lost. The anabolic effectiveness of parathyroid hormone has been established, and an exciting new prospect is presented of neutralising antibody against the osteocyte protein, sclerostin. The cellular actions of these two anabolic treatments differ, and the mechanisms will need to be kept in mind in devising their best use. On present evidence it seems likely that treatment with either of these anabolic agents will need to be followed by anti-resorptive treatment in order to maintain bone that has been restored. No matter how effective anabolic therapies for the skeleton become, it seems highly likely that there will be a continuing need for safe, effective anti-resorptive drugs.

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Interaction between Muscle and Bone: Hiroshi Kaji; J Bone Metab 2014;21(1):29-40.
Published online February 28, 2014; DOI: https://doi.org/10.11005/jbm.2014.21.1.29

The clinical significance of sarcopenia and osteoporosis has increased with the increase in the population of older people. Sarcopenia is defined by decreased muscle mass and impaired muscle function, which is related to osteoporosis independently and dependently. Numerous lines of clinical evidence suggest that lean body mass is positively related to bone mass, which leads to reduced fracture risk. Genetic, endocrine and mechanical factors affect both muscle and bone simultaneously. Vitamin D, the growth hormone/insulin-like growth factor I axis and testosterone are physiologically and pathologically important as endocrine factors. These findings suggest the presence of interactions between muscle and bone, which might be very important for understanding the physiology and pathophysiology of sarcopenia and osteoporosis. Muscle/bone relationships include two factors: local control of muscle to bone and systemic humoral interactions between muscle and bone. As a putative local inducer of muscle ossification, we found Tmem119, a parathyroid hormone-responsive osteoblast differentiation factor. Moreover, osteoglycin might be one of the muscle-derived humoral bone anabolic factors. This issue may be important for the development of novel drugs and biomarkers for osteoporosis and sarcopenia. Further research will be necessary to clarify the details of the linkage of muscle and bone.

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