Bone health and physical activity in adolescents with juvenile idiopathic arthritis: a cross-sectional case-control study.

BACKGROUND: Adolescents with juvenile idiopathic arthritis (JIA) tend to engage in less physical activity than their typically developing peers. Physical activity is essential for bone development and reduced physical activity may detrimentally effect bone health. Thus, we examined differences in total body bone mineral content (BMC) and areal bone mineral density (aBMD) between adolescents with JIA and adolescent controls without JIA. We also examined associations between moderate-to-vigorous physical activity (MVPA), lean mass, and bone outcomes. METHODS: Participants included 21 adolescents with JIA (14 females, 7 males) and 21 sex- and age-matched controls aged 10-20 years. Assessments included: height; weight; triple-single-leg-hop distance (TSLH); MVPA by accelerometry; and total body BMC, aBMD, and lean mass measured using dual X-ray absorptiometry. Height-adjusted z-scores were calculated for BMC and aBMD and used for all analyses. Multiple linear mixed effects models examined group differences in BMC and aBMD, adjusting for sex, maturity, MVPA, TSLH, and lean mass. Participants clusters, based on sex and age (within 18 months), were considered random effects. RESULTS: Adolescents with JIA had lower total body aBMD z-scores [ß (95% CI); -0.58 (-1.10 to -0.07), p = 0.03] and BMC z-scores [-0.47 (-0.91 to -0.03), p = 0.04] compared with controls. Mean daily MVPA was 22.0 min/day lower in adolescents with JIA than controls; however, MVPA was not associated with aBMD [-0.01 (-0.01 to 0.01), p = 0.32] or BMC [0.00 (-0.01 to 0.00), p = 0.39]. Lean mass was positively associated with aBMD [0.05 (0.01 to 0.09) g/cm2, p = 0.03] and BMC [0.06 (0.03 to 0.10) g, p < 0.001]. CONCLUSION: Adolescents with JIA had lower total body aBMD and BMC compared with sex- and age-matched controls without JIA. Group differences in bone outcomes were not associated with the lower MVPA participation of adolescents with JIA. Despite this, physical activity should still be encouraged as it promotes physical well-being.

The association of FRAX with predictors of falls in the assessment of postmenopausal osteoporosis in Turkey: the fracture study of Turkey (FRACT study).

Although FRAX is used for fracture risk evaluation, this tool does not include balance and fall risk. The association between the predictors of falls and high FRAX scores we found in this study suggests that risk indicators for falls may add substantial value to FRAX by improving fracture risk prediction. PURPOSE: This observational, descriptive, and cross-sectional study aimed to assess the fall risk predictors and explore their association with FRAX in Turkish patients with postmenopausal osteoporosis. METHODS: Two hundred and nine (209) women with postmenopausal osteoporosis referred to the Fracture Liaison Service (FLS) at Istanbul University-Cerrahpasa were enrolled in the FRACT study (The Fracture Study of Turkey). Clinical risk factors were assessed using the FRAX tool. Tandem stance, Tandem walking, Timed up and go (TUG), and Chair stand tests were performed to assess balance and fall risk. RESULTS: Among patients with a mean age of 67.6 (± 9.7) years, 66 patients (31.6%) had osteoporosis without fractures and 143 patients (68.4%) had fragility fractures. The proportion of patients with poor performance of fall prediction tests was significantly higher in patients with a fragility fracture than those with osteoporosis alone. There was an inverse relationship between dynamic balance tests and the reported number of prior falls in the past year. FRAX score was higher in patients with impaired Tandem stance, Tandem walking, and TUG tests (p = 0.008, p = 0.035, p = 0.001, respectively). CONCLUSION: Assessment of fall risk predictors should be one of the major pillars in the physical evaluation of osteoporotic patients in the FLS setting. FRAX is a useful tool to determine the fracture risk of patients with both static and dynamic balance impairments. Combining balance assessment with FRAX may be an important step to optimize osteoporosis risk assessment.

Bone mineral density in adults with arthrogryposis multiplex congenita: a retrospective cohort analysis.

The primary objective of this study was to evaluate the prevalence of low femoral and lumbar spine bone mineral density (BMD) in adults with arthrogryposis multiplex congenita (AMC). We performed a retrospective cohort analysis of adults with AMC who were enrolled in the French Reference Center for AMC and in the Pediatric and Adult Registry for Arthrogryposis (PARART, NCT05673265). Patients who had undergone dual-energy X-ray absorptiometry (DXA) and/or vitamin D testing were included in the analysis. Fifty-one patients (mean age, 32.9 ± 12.6 years) were included; 46 had undergone DXA. Thirty-two (32/51, 62.7%) patients had Amyoplasia, and 19 (19/51, 37.3%) had other types of AMC (18 distal arthrogryposis, 1 Larsen). Six patients (6/42, 14.3%) had a lumbar BMD Z score less than - 2. The mean lumbar spine Z score (- 0.03 ± 1.6) was not significantly lower than the expected BMD Z score in the general population. Nine (9/40, 22.5%) and 10 (10/40, 25.0%) patients had femoral neck and total hip BMD Z scores less than - 2, respectively. The mean femoral neck (- 1.1 ± 1.1) and total hip (- 1.2 ± 1.2) BMD Z scores in patients with AMC were significantly lower than expected in the general population (p < 0.001). Femoral neck BMD correlated with height (rs = 0.39, p = 0.01), age (rs = - 0.315, p = 0.48); total hip BMD correlated with height (rs = 0.331, p = 0.04) and calcium levels (rs = 0.41, p = 0.04). Twenty-five patients (25/51, 49.0%) reported 39 fractures. Thirty-one (31/36, 86.1%) patients had 25-hydroxyvitamin D levels less than 75 nmol/l, and 6 (6/36, 16.7%) had 25-hydroxyvitamin D levels less than 75 nmol/l. Adults with AMC had lower hip BMD than expected for their age, and they more frequently showed vitamin D insufficiency. Screening for low BMD by DXA and adding vitamin D supplementation when vitamin D status is insufficient should be considered in adults with AMC, especially if there is a history of falls or fractures.

Comprehensive analysis of circRNA expression profiles in postmenopausal women differing in bone mineral density.

Postmenopausal osteoporosis (PMOP) seriously endangers the bone health of older women. Although there are currently indicators to diagnose PMOP, early diagnostic biomarkers are lacking. Circular ribonucleic acid (circRNA) has a stable structure, regulates gene expression, participates in the pathological process of disease, and has the potential to become a biomarker. The purpose of this study was to investigate circRNAs that could be used to predict patients with early PMOP. Ribonucleic acid (RNA) sequencing was performed on peripheral blood leukocytes from 15 female patients to identify differential circRNAs between different groups. Using bioinformatics analysis, enrichment analysis was performed to discover relevant functions and pathways. CircRNA-micro ribonucleic acid (miRNA) interaction analysis and messenger ribonucleic acid (mRNA) prediction and network construction help us to understand the relationship between circRNA, miRNA, and mRNA. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to validate the gene expression of candidate circRNAs. We screened out 2 co-expressed differential circRNAs, namely hsa_circ_0060849 and hsa_circ_0001394. By analyzing the regulatory network, a total of 54 miRNAs and 57 osteoporosis-related mRNAs were identified, which, as potential downstream target genes of hsa_circ_0060849 and hsa_circ_0001394, may play a key role in the occurrence and development of PMOP. The occurrence and development of PMOP is regulated by circRNAs, and hsa_circ_0060849 and hsa_circ_0001394 can be used as new diagnostic markers and therapeutic targets for early PMOP.

Deep learning in the radiologic diagnosis of osteoporosis: a literature review.

OBJECTIVE: Osteoporosis is a systemic bone disease characterized by low bone mass, damaged bone microstructure, increased bone fragility, and susceptibility to fractures. With the rapid development of artificial intelligence, a series of studies have reported deep learning applications in the screening and diagnosis of osteoporosis. The aim of this review was to summary the application of deep learning methods in the radiologic diagnosis of osteoporosis. METHODS: We conducted a two-step literature search using the PubMed and Web of Science databases. In this review, we focused on routine radiologic methods, such as X-ray, computed tomography, and magnetic resonance imaging, used to opportunistically screen for osteoporosis. RESULTS: A total of 40 studies were included in this review. These studies were divided into three categories: osteoporosis screening (n = 20), bone mineral density prediction (n = 13), and osteoporotic fracture risk prediction and detection (n = 7). CONCLUSIONS: Deep learning has demonstrated a remarkable capacity for osteoporosis screening. However, clinical commercialization of a diagnostic model for osteoporosis remains a challenge.

Relationship between circulating FSH levels and body composition and bone health in patients with prostate cancer who undergo androgen deprivation therapy: The BLADE study.

Background: Among its extragonadal effects, follicle-stimulating hormone (FSH) has an impact on body composition and bone metabolism. Since androgen deprivation therapy (ADT) has a profound impact on circulating FSH concentrations, this hormone could potentially be implicated in the changes of fat body mass (FBM), lean body mass (LBM), and bone fragility induced by ADT. The objective of this study is to correlate FSH serum levels with body composition parameters, bone mineral density (BMD), and bone turnover markers at baseline conditions and after 12 months of ADT. Methods: Twenty-nine consecutive non-metastatic prostate cancer (PC) patients were enrolled from 2017 to 2019 in a phase IV study. All patients underwent administration of the luteinizing hormone-releasing hormone antagonist degarelix. FBM, LBM, and BMD were evaluated by dual-energy x-ray absorptiometry at baseline and after 12 months of ADT. FSH, alkaline phosphatase, and C-terminal telopeptide of type I collagen were assessed at baseline and after 6 and 12 months. For outcome measurements and statistical analysis, t-test or sign test and Pearson or Spearman tests for continuous variables were used when indicated. Results: At baseline conditions, a weak, non-significant, direct relationship was found between FSH serum levels and FBM at arms (r = 0.36) and legs (r = 0.33). Conversely, a stronger correlation was observed between FSH and total FBM (r = 0.52, p = 0.006), fat mass at arms (r = 0.54, p = 0.004), and fat mass at trunk (r = 0.45, p = 0.018) assessed after 12 months. On the other hand, an inverse relationship between serum FSH and appendicular lean mass index/FBM ratio was observed (r = -0.64, p = 0.001). This is an ancillary study of a prospective trial and this is the main limitation. Conclusions: FSH serum levels after ADT could have an impact on body composition, in particular on FBM. Therefore, FSH could be a promising marker to monitor the risk of sarcopenic obesity and to guide the clinicians in the tailored evaluation of body composition in PC patients undergoing ADT. Funding: This research was partially funded by Ferring Pharmaceuticals. The funder had no role in design and conduct of the study, collection, management, analysis, and interpretation of the data and in preparation, review, or approval of the manuscript. Clinical trial number: clinicalTrials.gov NCT03202381, EudraCT Number 2016-004210-10.

Treatments given to cancer patients can cause negative side effects. For example, a treatment known as androgen deprivation therapy ­ which is used to reduce male sex hormone levels in prostate cancer patients ­ can lead to increased body fat percentage and decreased bone density. These adverse effects can have further negative impacts on patient health, such as increasing the risk of cardiovascular disease and fractures from falls from standing height or less, respectively. Understanding how androgen deprivation therapy contributes to these negative side effects may help clinicians better manage care and outcomes for patients with prostate cancer. Follicle stimulating hormone (or FSH for short) has roles in male and female reproduction but has also been linked to changes in body composition. For example, elevated FSH levels are associated with higher total fat body mass in post-menopausal women. While androgen deprivation therapy is known to alter FSH blood levels, the impact of this change in prostate cancer patients was not well understood. To investigate the effect of androgen deprivation therapy on FSH levels and body composition, Bergamini et al. used X-ray technology to measure total fat body mass in prostate cancer patients before and after undergoing 12 months of androgen deprivation therapy. The findings showed that patient FSH blood levels significantly decreased after 12 months of treatment. Higher FSH blood levels strongly correlated with increased total fat body mass after 12 months of treatment. The findings of this clinical trial suggest that FSH blood levels impact the body composition of patients undergoing androgen deprivation therapy. As a result, FSH blood levels may be a suitable biomarker for identifying patients that are more likely to develop obesity and are therefore at greater risk of complications such as cardiovascular disease.

"The least significant change on bone mineral density scan increased in patients with higher degrees of obesity".

BACKGROUND: The least significant change (LSC) threshold of 0.03 g/cm² is used to interpret bone mineral density (BMD) scans in the general population. Our working hypothesis was that the current LSC threshold would not be applicable in obese populations. AIMS: The aim of this study was to calculate the LSC in an obese population. METHODS: We performed an interventional study among 120 obesity patients, in whom two measurements of BMD were performed at 3 sites. Pairs of measures were used to calculate the LSC, using the Bland and Altman method. RESULTS: We calculated that the LSC was 0.046 g/cm² at the lumbar spine, 0.069 g/cm² at the femoral neck, and 0.06 g/cm² at the total hip. We also calculated the LSC for each class of obesity and observed an increase in LSC with increasing body mass index (BMI). We calculated a LSC of 0.05 g/cm² in patients with class 2 or class 3 obesity, whereas the LSC in patients with class 1 obesity is similar to the threshold used in the general population. DISCUSSION: In obese population, like BMD, LSC is higher than the threshold value of the general population, and increases with increasing BMI. CONCLUSION: LSC of 0.05 g/cm² could be used in clinical practice in patients with class 2 or 3 obesity. These findings should help to improve the interpretation of BMD scans in these patients and optimize their management. TRIAL REGISTRATION NUMBER: Comité de Protection des Personnes Ile-de France VII, France.

The Expression and Secretion Profile of TRAP5 Isoforms in Gaucher Disease.

BACKGROUND: Gaucher disease (GD) is caused by glucocerebrosidase (GCase) enzyme deficiency, leading to glycosylceramide (Gb-1) and glucosylsphingosine (Lyso-Gb-1) accumulation. The pathological hallmark for GD is an accumulation of large macrophages called Gaucher cells (GCs) in the liver, spleen, and bone marrow, which are associated with chronic organ enlargement, bone manifestations, and inflammation. Tartrate-resistant acid phosphatase type 5 (TRAP5 protein, ACP5 gene) has long been a nonspecific biomarker of macrophage/GCs activation; however, the discovery of two isoforms of TRAP5 has expanded its significance. The discovery of TRAP5's two isoforms revealed that it is more than just a biomarker of macrophage activity. While TRAP5a is highly expressed in macrophages, TRAP5b is secreted by osteoclasts. Recently, we have shown that the elevation of TRAP5b in plasma is associated with osteoporosis in GD. However, the role of TRAP isoforms in GD and how the accumulation of Gb-1 and Lyso-Gb-1 affects TRAP expression is unknown. METHODS: 39 patients with GD were categorized into cohorts based on bone mineral density (BMD). TRAP5a and TRAP5b plasma levels were quantified by ELISA. ACP5 mRNA was estimated using RT-PCR. RESULTS: An increase in TRAP5b was associated with reduced BMD and correlated with Lyso-Gb-1 and immune activator chemokine ligand 18 (CCL18). In contrast, the elevation of TRAP5a correlated with chitotriosidase activity in GD. Lyso-Gb-1 and plasma seemed to influence the expression of ACP5 in macrophages. CONCLUSIONS: As an early indicator of BMD alteration, measurement of circulating TRAP5b is a valuable tool for assessing osteopenia-osteoporosis in GD, while TRAP5a serves as a biomarker of macrophage activation in GD. Understanding the distinct expression pattern of TRAP5 isoforms offers valuable insight into both bone disease and the broader implications for immune system activation in GD.

Evaluation of a vibration modeling technique for the in-vitro measurement of dental implant stability.

The Advanced System for Implant Stability Testing (ASIST) is a device currently being developed to noninvasively measure implant stability by estimating the mechanical stiffness of the bone-implant interface, which is reported as the ASIST Stability Coefficient (ASC). This study's purpose was to determine whether changes in density, bonding, and drilling technique affect the measured vibration of a dental implant, and whether they can be quantified as a change in the estimated BII stiffness. Stability was also measured using RFA, insertion torque (IT) and the pullout test. Bone-level tapered implants (4.1 mm diameter, 10 mm length) were inserted in polyurethane foam as an artificial bone substitute. Samples were prepared using different bone densities (20, 30, 40 PCF), drilling sequences, and superglue to simulate a bonded implant. Measurements were compared across groups at a significance level of 0.05. The ASC was able to indicate changes in each factor as a change in the interfacial stiffness. IT and pullout force values also showed comparable increases. Furthermore, the relative difference in ISQ values between experimental groups was considerably smaller than the ASC. While future work should be done using biological bone and in-vivo systems, the results of this in-vitro study suggest that modelling of the implant system with a vibration-based approach may provide a noninvasive method of assessing the mechanical stability of the implant.

Prolonged bone health benefits for breast cancer patients following adjuvant bisphosphonate therapy: the BoHFAB study.

Adjuvant bisphosphonates are often recommended in postmenopausal women with early breast cancer at intermediate-to-high risk of disease recurrence, but the magnitude and duration of their effects on bone mineral density (BMD) and bone turnover markers (BTMs) are not well described. We evaluated the impact of adjuvant zoledronate on areal BMD and BTMs in a sub-group of patients who had completed the large 5-yr randomized Adjuvant Zoledronic Acid to Reduce Recurrence (AZURE) trial. About 224 women (recurrence free) who had completed the AZURE trial within the previous 3 mo were recruited from 20 UK AZURE trial sites. One hundred twenty had previously been randomized to zoledronate (19 doses of 4 mg over 5 yr) and 104 to the control arm. BMD and BTMs were assessed at sub-study entry, 6 (BTMs only), 12, 24, and 60 mo following the completion of AZURE. As expected, mean BMD, T-scores, and Z-scores at sub-study entry were higher in the zoledronate vs the control arm. At the lumbar spine, the mean (SD) standardized BMD (sBMD) was 1123 (201) and 985 (182) mg/cm2 in the zoledronate and control arms, respectively (P < .0001). The baseline differences in sBMD persisted at all assessed skeletal sites and throughout the 5-yr follow-up period. In patients completing zoledronate treatment, BTMs were significantly lower than those in the control arm (α- and ß-urinary C-telopeptide of type-I collagen, both P < .00001; serum intact pro-collagen I N-propeptide, P < .00001 and serum tartrate-resistant acid phosphatase 5b, P = .0001). Some offset of bone turnover inhibition occurred in the 12 mo following the completion of zoledronate treatment. Thereafter, during the 60 mo of follow-up, all BTMs remained suppressed in the zoledronate arm relative to the control arm. In conclusion, in addition to the known anti-cancer benefits of adjuvant zoledronate, there are likely to be positive, lasting benefits in BMD and bone turnover.

FRAX predicts cardiovascular risk in women undergoing osteoporosis screening: the Manitoba bone mineral density registry.

Osteoporosis and cardiovascular disease (CVD) are highly prevalent in older women, with increasing evidence for shared risk factors and pathogenesis. Although FRAX was developed for the assessment of fracture risk, we hypothesized that it might also provide information on CVD risk. To test the ability of the FRAX tool and FRAX-defined risk factors to predict incident CVD in women undergoing osteoporosis screening with DXA, we performed a retrospective prognostic cohort study which included women aged 50 yr or older with a baseline DXA scan in the Manitoba Bone Mineral Density Registry between March 31, 1999 and March 31, 2018. FRAX scores for major osteoporotic fracture (MOF) were calculated on all participants. Incident MOF and major adverse CV events (MACE; hospitalized acute myocardial infarction [AMI], hospitalized non-hemorrhagic cerebrovascular disease [CVA], or all-cause death) were ascertained from linkage to population-based healthcare data. The study population comprised 59 696 women (mean age 65.7 ± 9.4 yr). Over mean 8.7 yr of observation, 6021 (10.1%) had MOF, 12 277 women (20.6%) had MACE, 2274 (3.8%) had AMI, 2061 (3.5%) had CVA, and 10 253 (17.2%) died. MACE rates per 1000 person-years by FRAX risk categories low (10-yr predicted MOF <10%), moderate (10%-19.9%) and high (≥20%) were 13.5, 34.0, and 64.6, respectively. Although weaker than the association with incident MOF, increasing FRAX quintile was associated with increasing risk for MACE (all P-trend <.001), even after excluding prior CVD and adjusting for age. HR for MACE per SD increase in FRAX was 1.99 (95%CI, 1.96-2.02). All FRAX-defined risk factors (except parental hip fracture and lower BMI) were independently associated with higher non-death CV events. Although FRAX is intended for fracture risk prediction, it has predictive value for cardiovascular risk.

Rapid bone microarchitecture decline in older men with high bone turnover-the prospective STRAMBO study.

Older men with high bone turnover have faster bone loss. We assessed the link between the baseline levels of bone turnover markers (BTMs) and the prospectively assessed bone microarchitecture decline in men. In 825 men aged 60-87 yr, we measured the serum osteocalcin (OC), bone alkaline phosphatase (BAP), N-terminal propeptide of type I procollagen (PINP), and C-terminal telopeptide of type I collagen (CTX-I), and urinary total deoxypyridinoline (tDPD). Bone microarchitecture and strength (distal radius and distal tibia) were estimated by high-resolution pQCT (XtremeCT, Scanco Medical) at baseline and then after 4 and 8 yr. Thirty-seven men took medications affecting bone metabolism. Statistical models were adjusted for age and BMI. At the distal radius, the decrease in the total bone mineral density (Tt.BMD), cortical BMD (Ct.BMD), cortical thickness (Ct.Thd), and cortical area (Ct.Ar) and failure load was faster in the highest vs the lowest CTX-I quartile (failure load: -0.94 vs -0.31% yr-1, P < .001). Patterns were similar for distal tibia. At the distal tibia, bone decline (Tt.BMD, Ct.Thd, Ct.Ar, Ct.BMD, and failure load) was faster in the highest vs the lowest tDPD quartile. At each skeletal site, the rate of decrease in Tb.BMD differed between the extreme OC quartiles (P < .001). Men in the highest BAP quartile had a faster loss of Tt.BMD, Tb.BMD, reaction force, and failure load vs the lowest quartile. The link between PINP and bone decline was poor. The BTM score is the sum of the nos. of the quartiles for each BTM. Men in the highest quartile of the score had a faster loss of cortical bone and bone strength vs the lowest quartile. Thus, in the older men followed prospectively for 8 yr, the rate of decline in bone microarchitecture and estimated bone strength was 50%-215% greater in men with high bone turnover (highest quartile, CTX-I above the median) compared to the men with low bone turnover (lowest quartile, CTX-I below the median).

Bone loss after discontinuation of denosumab: the devil is in the details.

A 47-year-old postmenopausal woman with osteoporosis was treated with denosumab, which was discontinued due to side effects. She was therefore transitioned to a yearly intravenous infusion of zoledronic acid. An increase in bone turnover markers together with bone loss at the lumbar spine was observed before the second infusion, suggesting an overshooting of bone resorption due to denosumab discontinuation. On physical examination, the patient was restless and reported having lost about 10 kg since the last visit. A solitary left inferior thyroid nodule was noted on neck palpation. Circulating thyroid hormone levels were elevated, with suppressed thyroid-stimulating hormone. A thyroid scan showed increased uptake in the left inferior nodule with suppression of the remainder of the thyroid gland. A diagnosis of hyperthyroidism due to toxic adenoma was made. The patient was treated with radioactive iodine ablation, with consequent complete normalization of thyroid function. She continued yearly treatment with zoledronic acid. She remained clinically well with no further fractures. Bone turnover markers were appropriately suppressed and bone mineral density increased in the spine and hip. This case illustrates how the overshooting phenomenon following denosumab discontinuation may be compounded by the development of secondary conditions, which can result in suboptimal response to antiresorptive osteoporosis medications.

Raman spectroscopic analysis for osteoporosis identification in humans with hip fractures.

Osteoporosis is a significant health concern. While multiple techniques have been utilized to diagnose this condition, certain limitations still persist. Raman spectroscopy has shown promise in predicting bone strength in animal models, but its application to humans requires further investigation. In this study, we present an in vitro approach for predicting osteoporosis in 10 patients with hip fractures using Raman spectroscopy. Raman spectra were acquired from exposed femoral heads collected during surgery. Employing a leave-one-out cross-validated linear discriminant analysis (LOOCV-LDA), we achieved accurate classification (90 %) between osteoporotic and osteopenia groups. Additionally, a LOOCV partial least squares regression (PLSR) analysis based on the complete Raman spectra demonstrated a significant prediction (r2 = 0.84, p < 0.05) of bone mineral density as measured by dual X-ray absorptiometry (DXA). To the best of our knowledge, this study represents the first successful demonstration of Raman spectroscopy correlating with osteoporotic status in humans.

Systematical mutational analysis of teriparatide on anti-osteoporosis activity by alanine scanning.

Osteoporosis is a progressive systemic skeletal disease that decreases bone density and bone quality, making them fragile and easy to break. In spite of effective anti-osteoporosis potency, teriparatide, the first anabolic medications approved for the treatment of osteoporosis, was proven to exhibit various side effects. And the relevant structure-activity relationship (SAR) of teriparatide was in need. In this work, we performed a systematical alanine scanning against teriparatide and synthesized 34 teriparatide derivatives. Their biological activities were evaluated and the importance of each residue for anti-osteoporosis activity was also revealed. A remarkable decrease in activity was observed for alanine replacement of the residue Gly12, His14, Ser17, Arg20 and Leu24, showcasing the important role of these residues in teriparatide on anti-osteoporosis activity. On contrary, when Gly13 and Gln30 were mutated to Ala, the peptide derivatives exhibited the significantly increased activities, demonstrating that these two residues could be readily replaced. Our research expanded the peptide library of teriparatide analogues and presented a potential opportunity for designing the more powerful anti-osteoporosis peptide agents.

Assessment of Biochemical Bone Turnover Markers in Polish Healthy Children and Adolescents.

BACKGROUND: Assessing bone turnover in paediatric populations is crucial for understanding the physiological changes occurring during skeletal development and identifying potential abnormalities. The objective of this study was to assess osteocalcin (OC), bone alkaline phosphatase (BALP), and C-terminal telopeptide of type I collagen (CTX-I) levels reflecting bone formation and resorption for age and sex in Polish healthy children and adolescents. MATERIALS AND METHODS: A total of 355 healthy normal-weight children and adolescents (46.5% girls) aged 1-18 years old were recruited. Total body less head (TBLH) and spine L1-L4 were used in children to assess bone mineral density (BMD) by dual-energy X-ray absorptiometry (DXA). Bone marker concentrations were determined by immunoenzymatic methods. RESULTS: Bone marker levels in girls and boys started with higher values in the first year of life and subsequently decreased until reaching a nadir during the prepubertal period. The pubertal peak values of bone markers were reached at 11-13 years old in boys and at 9-11 years old in girls. After puberty, the adolescents showed a gradual decline in bone marker concentrations to the values observed in adults. We found positive correlations between OC level and TBLH-BMD (r = 0.329, p = 0.002), TBLH-BMD Z-score (r = 0.245, p = 0.023), and L1-L4 BMD (r = 0.280, p = 0.009) in the prepubertal group. CONCLUSIONS: We showed serum levels of bone turnover markers-BALP, OC, and CTX-I-in relation to age and sex in healthy Polish children and adolescents. The age intervals of these markers for girls and boys aged 1-18 years old may be clinically useful in the assessment of bone metabolism in individuals with skeletal disorders.

Predicting Tibia-Fibula Geometry and Density From Anatomical Landmarks Via Statistical Appearance Model: Influence of Errors on Finite Element-Calculated Bone Strain.

State-of-the-art participant-specific finite element models require advanced medical imaging to quantify bone geometry and density distribution; access to and cost of imaging is prohibitive to the use of this approach. Statistical appearance models may enable estimation of participants' geometry and density in the absence of medical imaging. The purpose of this study was to: (1) quantify errors associated with predicting tibia-fibula geometry and density distribution from skin-mounted landmarks using a statistical appearance model and (2) quantify how those errors propagate to finite element-calculated bone strain. Participant-informed models of the tibia and fibula were generated for thirty participants from height and sex and from twelve skin-mounted landmarks using a statistical appearance model. Participant-specific running loads, calculated using gait data and a musculoskeletal model, were applied to participant-informed and CT-based models to predict bone strain using the finite element method. Participant-informed meshes illustrated median geometry and density distribution errors of 4.39-5.17 mm and 0.116-0.142 g/cm3, respectively, resulting in large errors in strain distribution (median RMSE = 476-492 µÎµ), peak strain (limits of agreement =±27-34%), and strained volume (limits of agreement =±104-202%). These findings indicate that neither skin-mounted landmark nor height and sex-based predictions could adequately approximate CT-derived participant-specific geometry, density distribution, or finite element-predicted bone strain and therefore should not be used for analyses comparing between groups or individuals.

Significant Inverse Correlation of Serum Levels of Osteoprotegerin (OPG) and Transferrin Saturation in Thalassemia Dependent Transfusion (TDT) Patients.

BACKGROUND: Osteoporosis is a major problem in transfusion-dependent thalassemia patients (TDT) patients. Osteoprotegerin (OPG) is one of several bone markers that are closely associated with osteoporosis in TDT patients. OPG is a glycoprotein that functions as a feedback receptor for the Receptor Activator of Nuclear Factor kappa B Ligand (RANKL), which is an alpha tumor necrosis factor receptor. One of the causes of decreased bone mass density is iron toxicity, which can be identified by showing elevated transferrin saturation. Bone mass dual X-ray absorptiometry (DEXA) is a gold standard for the diagnosis of osteoporosis, these procedures are not commonly available in Indonesia. This study was conducted to analyze the correlation between serum levels of OPG and transferrin saturation in TDT patients. METHODS: A correlational study with a cross-sectional approach analyzed data from TDT patients at Hemato-Oncology Medic Outpatient Clinic, Hasan Sadikin General Hospital, Bandung, Indonesia. Primary data were obtained through blood sampling and anthropometry measurement while secondary data were obtained from the patient's medical records. OPG and transferrin saturation levels were assessed using the ELISA method. Research data were analyzed using the rank Spearman correlation test. RESULTS: Data were collected from 51 research subjects (30 women dan 21 men). The median OPG level was 380 (170-1230) pg/mL and the median transferrin saturation level was 89.4 (66.7 - 96.2)%. Analysis of correlation showed a significant correlation between and transferrin saturation level with a coefficient value of r -0.539 and p-value <0.001. CONCLUSION: There was a significant inverse correlation between OPG with transferrin saturation in TDT patients.