BACKGROUND:Myostatin (MSTN) is a well-known negative regulator of skeletal muscle growth, and its pharmacological blockade, such as with follistatin (FST), an endogenous MSTN inhibitor, is under active investigation as a treatment for muscle-wasting conditions. However, the dynamics of MSTN signaling during in vitro myogenesis and its modulation by culture conditions remain incompletely understood. METHODS:Primary myoblasts were isolated from wild-type (WT), Mstn-/-, and FST transgenic (F66) mice to evaluate the effects of MSTN inhibition on myotube formation. Myoblasts were differentiated on Matrigel-coated surfaces in the presence of horse serum. Myotube maturation was evaluated by confocal microscopy and reverse transcription-polymerase chain reaction; protein synthesis was assessed using a puromycin incorporation assay; and MSTN concentrations in serum were quantified by enzyme-linked immunosorbent assay. RESULTS:Mstn expression peaked at 24 hr of differentiation, coinciding with early myotube formation, and progressively declined as myotubes matured. Both Mstn-/- and F66 myotubes showed increased thickness and protein synthesis compared to WT controls, with more pronounced effects observed in F66 myotubes. Consistent with this, F66 myotubes also displayed higher expression of myogenic maturation markers. Notably, horse serum used in the culture medium contained detectable levels of MSTN, which may have partially restored MSTN signaling in Mstn-/- cultures and masked the full knockout phenotype. CONCLUSIONS:FST overexpression induces greater myotube hypertrophy and protein synthesis than Mstn deletion, likely due to its broader inhibition of both endogenous and serum-derived MSTN. These findings highlight the importance of serum composition in interpreting phenotypes from in vitro knockout models targeting secreted factors such as MSTN.
Glucagon-like peptide-1 (GLP-1) analogs, originally developed as antidiabetic agents, have emerged as groundbreaking drugs for treating obesity, following reports of their remarkable weight-reducing effects. With growing recognition of obesity as a disease in modern society and a sharp rise in its prevalence, pharmacological interventions are now being actively pursued. However, due to their mechanism of action, primarily appetite suppression, GLP-1 analogs have been associated with various adverse effects. Most notably, muscle loss - which may be related to reduced nutritional intake - has become an important issue in the long-term management of patients undergoing GLP-1 therapy. This has drawn attention to myostatin (MSTN) inhibitors for their ability to significantly increase muscle mass. These agents are now being explored not only as a strategy to offset the side effects of GLP-1 analogs, but also as direct therapeutics for a range of metabolic disorders, including obesity and diabetes. In this review, we discuss the emerging therapeutic potential of MSTN inhibitors and examine current clinical trials investigating their use alone or in combination with GLP-1 analogs in metabolic disorders.
BACKGROUND:The association between diet quality (DQ) and osteoarthritis (OA) among the Asian population is unclear. Even within this population, the associations between DQ and OA may differ by region. We examined the relationship between DQ and radiologic knee OA (RKOA) among Koreans, stratifying participants by residential area. METHODS:This cross-sectional study used data from the Korea National Health and Nutrition Examination Survey conducted in 2013. A total of 2,222 participants aged 50 years old and older with available data on RKOA and DQ were analyzed. DQ was evaluated using the Korean Healthy Eating Index (KHEI). RKOA was diagnosed via radiography and defined as having a Kellgren-Lawrence grade ≥2 in the knee. Participants were categorized by residential region: metropolitan cities, small to medium-sized cities, or rural areas. The odds ratios for RKOA across the three regions were analyzed using multiple logistic regression, adjusting for confounding factors. RESULTS:High KHEI scores were associated with lower odds of RKOA (P for trend=0.03). This association was primarily observed in residents of metropolitan cities, particularly among men (P for trend=0.02). CONCLUSIONS:Better DQ is associated with reduced odds of RKOA in older Korean adults living in metropolitan areas.
Background: The survival impact of bisphosphonates (BPs) remains uncertain, particularly in East Asian populations, where new-user analyses have been limited.Methods: This was a retrospective, new-user cohort study using the Korean National Health Insurance Service–National Sample Cohort (2002–2011). We identified new users of BPs (N=41,854), and a 1:1 age-matched control group (N=41,854) among women aged ≥ 50 years. Participants were followed for all-cause mortality for up to 10 years. Multivariable Cox proportional hazards models were used to calculate hazard ratios (HRs), adjusting for age and the Charlson Comorbidity Index.Results: A total of 83,708 women were included. Compared with the control group, the risk of all-cause mortality was lower in BP group. BP users showed adjusted HR of 0.47 (95% confidence interval, 0.44–0.49; P<0.001) compared to controls. Conclusions: In this large, nationwide Korean cohort, initiating BPs was associated with a reduced risk of all-cause mortality in women aged 50 and older. These findings suggest that BPs may have survival benefits beyond fracture prevention.
BACKGROUND:Bone mineral density (BMD) is a key predictor of fracture risk in postmenopausal women. Evidence on the influence of fat and lean mass (LM) on BMD remains contradictory. This study aimed to assess the associations between BMD at different sites (whole-body, upper, and lower limbs) and anthropometric and body composition variables measured by dual energy X-ray absorptiometry (DXA) in postmenopausal women. METHODS:A cross-sectional study was conducted on 308 healthy postmenopausal women. Anthropometric data and whole-body DXA scans were used to measure BMD, total fat mass (FM), LM, appendicular LM index (ALMI), and abdominal fat. Pearson or Spearman correlation analyses were used according to variable distribution, and a correlation matrix along with variance inflation factor analyses was used to reduce 18 variables to a final set of 5. Multiple linear regression models were built for BMD at each site. RESULTS:Age was negatively correlated with BMD at all sites. Total LM and ALMI demonstrated positive correlations with BMD, whereas body mass index (BMI) and abdominal fat exhibited weaker positive associations. In multivariable analyses, age was negatively associated with whole-body BMD, while total LM was positively associated. For lower-limb BMD, age and total LM were significant predictors, with BMI showing a positive but weaker association. For upper-limb BMD, total LM, and ALMI were all positively associated. The models demonstrated satisfactory fit (adjusted R², 0.341-0.438; global P<0.0001). CONCLUSIONS:Age and total LM were independently and consistently associated with BMD in postmenopausal women, whereas FM and BMI had a limited impact.
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.
BACKGROUND:Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome characterized by hypophosphatemia and osteomalacia, resulting from excessive production of fibroblast growth factor 23 by mesenchymal tumors. Although various imaging techniques are used to localize the tumor, the rarity of the disease poses significant challenges in tumor detection. METHODS:After retrospectively analyzing 25 TIO patients who visited the Severance bone and mineral clinic between 2004 and 2024, we added all reported TIO cases in Korea by searching PubMed, Embase, and Web of Science. Using the PRISMA method, an additional 14 reports comprising 22 patients were included. RESULTS:Among the 47 patients, 25 (53.2%) were male, with a median age of 52 years. Tumors were most commonly located in the lower extremities (57.5%), with a median size of 1.9 cm. Surgical resection, including radiofrequency ablation, was performed in 45 patients; reoperation was required in 26.7% (12/45) due to residual tumors. After gallium scans were covered by insurance, 83.3% (25/30) of patients underwent gallium-based imaging for tumor localization with 77.3% of tumors successfully localized in initial scan. Of the five patients with negative initial scans, four (80%) showed positive findings on a second scan conducted 1 to 2 years later. CONCLUSIONS:Although gallium scans are the most commonly employed imaging modality for detecting tumors responsible for TIO, localization remains challenging due to the small tumor size, potential for widespread anatomical distribution, and prolonged diagnostic delay. Repeating gallium imaging can yield positive results in previously negative cases, and additional imaging modalities may be necessary to facilitate accurate localization.
Background: Posterior spinal fusion is performed for severe adolescent idiopathic scoliosis (AIS), with bone graft playing a critical role in achieving solid fusion. Iliac crest bone graft (ICBG) is the gold standard but has donor site morbidity, leading to increased use of non-ICBG. This study compared the effectiveness and safety of ICBG and non-ICBG bone grafts in AIS.Methods: This meta-analysis included 23 studies with 3,350 patients, categorized into ICBG and non-ICBG groups. The primary outcome was fusion rate; secondary outcomes were implant-related complication rate, infection rate, donor site pain, blood loss, and operation time. A proportion meta-analysis was conducted to estimate binary outcomes, and a weighted mean model was used to estimate continuous variables.Results: The fusion rate was 97% (95% confidence interval [CI], 93-99) in ICBG group and 97% (95% CI, 95-98) in non-ICBG group. Implant-related complications occurred in 5% (95% CI, 3-7) and 4% (95% CI, 2-6) of each group, while surgical site infections occurred in 3% (95% CI, 2-7) and 2% (95% CI, 1-3). Donor site pain was observed exclusively in ICBG group, with a prevalence of 49% (95% CI, 3–97). Estimated pooled blood loss was 1,461.10 mL (95% CI, 545.30-2,376.90) in ICBG group and 1,047.45 mL (95% CI, 666.92-1,427.99) in non-ICBG group. The estimated pooled operation time was 246.77 (95% CI, 221.74-271.80) and 232.37 (95% CI, 194.88-269.86) for each group.Conclusions: Considering both ICBG and non-ICBG demonstrated high fusion rates and low complication rates, non-ICBG grafts may serve as an effective and safe alternative to ICBG, minimizing morbidity, donor site pain, and blood loss.
BACKGROUND:Calcium is essential for bone health, but its intake remains inadequate in populations with limited dairy consumption. Fish bones, abundant in calcium and phosphorus, represent a largely untapped natural resource for dietary calcium supplementation. The application of high-energy ball milling (HEM) presents a promising strategy to enhance calcium bioavailability by producing particles at the nanoscale. METHODS:This study used HEM to convert fish bones from Euthynnus affinis (tuna) and Lutjanus sp. (snapper) into nanoparticles. The resulting powder was analyzed for particle size, morphology, crystallinity, thermal, flowability, hygroscopicity, mineral composition, and proximate constituents. RESULTS:The HEM process successfully reduced the particle size of snapper and tuna bone powder to 729.83 and 847.93 nm, respectively, without altering their crystallinity. Morphological analysis revealed irregularly shaped particles, while thermal analysis indicated an exothermic decomposition pattern. No hygroscopic properties were observed in any of the samples. The nanonization process preserved the intrinsic mineral composition of the fish bones. Calcium/Phosphorus ratios remained >1.8. Elemental analysis confirmed high levels of calcium, phosphorus, and essential minerals such as potassium, magnesium, and sodium, while the protein and ash contents met nutritional standards. CONCLUSIONS:Fish bone-derived nanoparticles produced via HEM exhibit advantageous physicochemical characteristics for nutraceutical applications and represent a promising source of bioavailable calcium to support bone health.
BACKGROUND:Hypothyroidism is the most common thyroid dysfunction, and current evidence suggests that it increases the risk of osteoporosis in these patients. Assessing the level of osteoporosis awareness and understanding among hypothyroid patients is an important requirement for implementing preventive interventions to maintain bone health. METHODS:Thyroid-stimulating hormone, thyroxine, and 25-hydroxy-vitamin D levels were recorded along with the patients' demographics. Osteoporosis awareness was assessed with the osteoporosis awareness scale (OAS), and knowledge level was assessed with the revised osteoporosis knowledge test (R-OKT). Health beliefs related to osteoporosis were evaluated using the osteoporosis health belief scale (OHBS). RESULTS:The median (interquartile range) values for OAS and R-OKT of 348 patients were calculated as 66.0 (32.0) and 9.0 (5.0), respectively. Female patients had higher OAS scores (P<0.001), OHBS benefits of exercise (P=0.002), and calcium intake (P<0.001) subscores compared to males. The distribution of OAS, R-OKT, and OHBS total and susceptibility scores differed significantly across education categories (P<0.001). The linear regression model revealed significant predictors of OAS score variation, including gender (β=-0.27, P<0.001), education (β=0.09, P=0.045), and osteoporosis knowledge (β=0.49, P<0.001). CONCLUSIONS:Patients with hypothyroidism, particularly males and those with lower educational attainment, lack adequate knowledge and awareness regarding osteoporosis. To better comprehend and manage osteoporosis, targeted educational initiatives are required for this vulnerable group.
The 17th Sarcopenia, Cachexia, and Wasting Disorders Conference, held from December 6 to 8, 2024, in Washington, DC, showcased groundbreaking advancements in understanding and managing muscle wasting conditions. Drawing on the lecture notes and presentations of internationally recognized experts who spoke at the meeting, this review highlights key insights and recent developments discussed during the conference. This review focuses on sarcopenia, cancer cachexia, and other wasting disorders linked to chronic diseases. Key discoveries included the identification of the Macroautophagy and YouTH Optimizer pathway in muscle regulation, the role of ectodysplasin A2 receptor-nuclear factor-κB-inducing kinase signaling in muscle atrophy, and the impact of mitochondrial dysfunction on systemic health. Advancements in diagnostic tools, including artificial intelligence-powered imaging and novel biomarkers, are transforming the detection and management of these conditions. Emerging therapeutic strategies, such as glucagon-like peptide 2-based treatments, selective androgen receptor modulators, and cytokine inhibitors, are reshaping the therapeutic landscape. The conference underscored the importance of precision medicine, integrating molecular insights with personalized care approaches, and emphasized multidisciplinary rehabilitation to optimize patient outcomes. The conference also highlighted promising clinical advancements, including the HIPGEN trial on placental-expanded stromal cells for muscle regeneration in hip fracture patients and the ponsegromab study targeting growth/differentiation factor-15 inhibition to mitigate cancer cachexia-associated muscle wasting. This review highlights the integration of basic science, innovative diagnostics, and clinical applications as a promising framework for addressing the complex challenges posed by muscle-wasting disorders. As the field progresses, these insights offer hope for improving the quality of life and survival of affected patients.
Tyrosine kinases (TK) are critical enzymes involved in cellular processes in the joints, such as proliferation, differentiation, and apoptosis. These inhibitors target key pathways involved in cartilage degeneration and inflammation, offering hope for improved management of these conditions. This review examines the role of TK inhibitors in modulating chondrocyte activity and explores their therapeutic potential in cartilage-related diseases, including rheumatoid arthritis (RA) and osteoarthritis (OA). A search has been conducted across several relevant publications using the terms cartilage regeneration, chondrocyte activity, OA, RA, and TK inhibitors in PubMed and Google Scholar to construct this review. TK inhibitors have the potential to manage inflammatory and degenerative joint disorders. Tofacitinib, gefitinib, imatinib and other TK inhibitors have anti-inflammatory effects through various pathways, aiding in treating cartilage diseases. Tofacitinib and baricitinib are already approved for RA, while other TK inhibitors are under continuous investigation for approval in RA and OA. Nonetheless, certain obstacles like serious side effects, limited joint-specificity, and inadequate clinical research impede their utilization. Despite these challenges, TK inhibitors signify a promising treatment strategy for joint diseases, presenting the potential to improve disease management strategies and promote cartilage regeneration.
BACKGROUND:Prodromal symptoms might lead to an early diagnosis of atypical femoral fracture (AFF). However, incomplete AFF can progress to complete fractures because they are often misdiagnosed as degenerative diseases such as lumbar canal stenosis or knee and hip osteoarthritis. The purpose of this study was to examine how many AFFs are misdiagnosed as degenerative diseases and the characteristics of the site of prodromal symptoms in a multicenter study. METHODS:We retrospectively analyzed the medical records of patients with AFFs at two institutions. In addition, a survey was sent to affiliated institutions to collect data on prodromal symptoms. RESULTS:Analysis in two institutions revealed 46 AFFs in 35 patients. Seventeen fractures were associated with localized prodromal symptoms in the groin or lateral thigh (conventional type), and 12 fractures had prodromal symptoms not localized to the fracture site, such as widespread lateral thigh, knee, or lateral lower leg (modified type). Eleven fractures were misdiagnosed as degenerative diseases. The survey of 11 affiliated institutions revealed that prodromal pain was reported in 29 of 49 AFFs. Nineteen fractures were associated with modified prodromal pain, and 9 fractures were misdiagnosed as degenerative diseases. CONCLUSIONS:Twenty-one percent of AFFs were misdiagnosed with degenerative diseases. All of the misdiagnosed cases were associated with prodromal symptoms. We believe that the prodromal symptoms of AFF are diverse and very similar to those of degenerative diseases, which may have caused the misdiagnosis.
BACKGROUND:This study evaluated the correlation between the degree and duration of thyroid-stimulating hormone (TSH) suppression and changes in bone mineral density (BMD) in patients who underwent surgery for differentiated thyroid carcinoma (DTC). METHODS:We included 65 women who underwent surgery for DTC and had at least two BMD measurements. Changes in BMD were statistically analyzed with a focus on postmenopausal women. RESULTS:The mean patient age was 52.2 years. During the follow-up period, 10 patients (15.4%) received osteoporosis treatment, and six (9.2%) experienced fractures. Analysis of 50 postmenopausal women revealed significant decreases in lumbar spine BMD (P=0.007), femoral neck BMD (P=0.008), and total hip BMD (P=0.010). Patients with TSH suppression <0.5 mU/L exhibited a 1.24%/y decrease in lumbar spine BMD, showing a marked reduction compared to a 0.33%/y decrease in BMD in the group with TSH ≥0.5 mU/L (P=0.025). Linear regression analysis comparing the duration of TSH suppression revealed a significant correlation with lumbar spine BMD (P<0.001). However, no correlation was observed between TSH suppression and decreased femoral neck BMD. Although not significant, the reduction in BMD in the lumbar spine was greater in the calcium and vitamin D non-supplementation group than in the supplementation group (1.31%/y vs. 0.71%/y; P=0.349). CONCLUSIONS:Prolonged aggressive TSH suppression significantly affects lumbar spine BMD in patients with DTC. These findings highlight the need to balance TSH suppression with the risk of bone health deterioration, particularly in postmenopausal women.
BACKGROUND:Sarcopenia is an age-related disease, and is assumed to be associated with systemic inflammation. We examined the relationship between the neutrophil-to-lymphocyte ratio (NLR), an easily accessible inflammatory marker, and sarcopenia in older adults. METHODS:This retrospective cross-sectional study, medical records of patients visiting a tertiary hospital's health check-up center were analyzed. The study included older adults aged 60 and over, and who had their grip strength, skeletal muscle mass, and complete blood count with differential tests measured. In this study, sarcopenia was defined as the presence of both low muscle mass and weak grip strength according to the Asian Working Group for Sarcopenia 2019 criteria. RESULTS:Of the 2,385 participants, 74 participants (3.10%) had sarcopenia. The non-sarcopenia group was younger than the sarcopenia group (mean age, 65.8±5.4 vs. 73.2±7.5). The average NLR of participants without sarcopenia was 1.75±0.97 and the average NLR of participants with sarcopenia was 2.08±1.11 (P=0.004). The number of participants with sarcopenia increased across higher NLR quintile (P for trend=0.016), as well as those with low skeletal muscle mass (P for trend<0.001) and weak grip strength (P for trend=0.009). CONCLUSIONS:Older adults with a high NLR may be considered for sarcopenia screening.
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.
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.
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.
BACKGROUND:The adequacy of calcium from food consumption is difficult to meet because of its low absorption rate, causing an increased risk of osteoporosis. One of the ways to increase calcium absorption is to increase its solubility by decreasing its particle size. This study aimed to observe the influence of particle size and mineral composition of various fish bone powders on bone density enhancement after oral administration to corticosteroid-induced osteoporosis rats. METHODS:The test stages carried out include manufacturing fish bone flour and nanonization, characterization (particle size and nutritional content), conducting experimental tests on rats using blood serum samples, and observing bone growth and density. The types of fish studied were catfish, snakehead fish, mackerel, and snapper. RESULTS:Nanonization processing has been proven to reduce the size of flour particles, increase its nutritional and mineral content, and maximize the calcium absorption rate in rats. The results of the test on experimental animals induced osteoporosis showed that rats given the intervention of milling snapper fish bone meal produced the best outcomes in body length, body mass index, calcium, magnesium, and serum phosphorus (P<0.05). While in bone parameters, catfish bone meal was the most optimal in encouraging bone density percentage. CONCLUSIONS:In conclusion, to increase serum minerals and bone density optimally, in addition to reducing particle size, the ratio of mineral content also needs to be considered.
