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Abstract Background Teriparatide (TPTD) is a widely used anabolic agent for the treatment of osteoporosis. Several factors have been identified to be related to bone mineral density (BMD) increase in anti-osteoporosis treatment with other agents; however, there has been no systematic analysis to summarize the associated determinants of BMD reaction to daily teriparatide treatment. Methods In this retrospective study, we performed a comprehensive investigation involving not only clinical data but also several relevant lifestyle factors to be examined for their potential contribution to BMD response. This post-hoc analysis included 258 post-menopaused patients with osteoporosis who received TPTD at 20 µg/day for 12 months. Univariate and multivariate analyses were conducted to distinguish the response variables of lumbar spine (LS) BMD transformation, the principal outcome measure of efficacy, from the baseline at 12 months. Results Twelve months of TPTD treatment resulted in an absolute 0.39 ± 0.37 increase in T-score of LS BMD. Gastrointestinal disease, prior bisphosphonate or glucocorticoid treatment, no vitamin K2 supplementation, low levels of serum 25(OH)D and PINP, weak increment of PINP and β-CTX at 3 months, unhealthy lifestyle (excessive smoking, tea, coffee, and drinking), vegetarian diet pattern, low ALT level, and high BMD at baseline were determined by univariate analyses to be related to the weak reaction of TPTD treatment (P

Abstract Background Atypical femur fractures are a rare occurrence, especially in bisphosphonate-naïve men, and merit reporting owing to their unusual presentation and clinical implications. This case report highlights a unique instance of atypical femur fractures in a 73-year-old male with no prior bisphosphonate exposure. Case presentation The patient, a 73-year-old Indian male with no history of bisphosphonate use, presented with left thigh pain and swelling following a minor fall. Radiographic assessment unveiled a closed left mid diaphyseal femoral shaft fracture. Subsequent imaging revealed an impending fracture in the contralateral femur. A comprehensive diagnostic evaluation, encompassing radiographic analysis, laboratory tests, and clinical assessment confirmed the diagnosis. Surgical management via intramedullary nailing was pursued for both fractures. Notably, the patient’s medical history was characterized by radiographic manifestations, the infrequent occurrence of atypical femur fractures in men, and associated risk factors. Treatment encompassed anabolic bone therapy employing teriparatide, alongside discontinuation of antiresorptive agents. Conclusions This case underscores the significance of considering atypical femur fractures in older individuals with limited trauma history. It accentuates the role of anabolic agents in the therapeutic regimen and contributes to the evolving understanding of atypical femur fractures. The report underscores the need for vigilant monitoring and tailored management strategies in similar cases, thereby enhancing clinical practice and patient care.

Trauma, tooth loss, cancer surgery, congenital malformations, periodontal disease, and oral-maxillofacial surgery are all major causes of bone loss, deformity, or fracture. Bone healing is a physiologically complicated process that also incorporates mechanical factors. Too many doubts concerning bone regeneration and the conditions that promote it have persisted for far too long. To assess the impact of systemic teriparatide therapy on mandibular bone defects healing.Forty male albino rats were randomly divided into two groups: the control group and the treatment group, with 20 rats per group. All rats had the same surgical technique. A small hole was created in the mandible, measuring 3 mm in diameter and 3 mm in depth, and then left unoccupied. The treatment group received a daily subcutaneous injection of Teriparatide at a dose of 10 µg/kg. Animals were subjected to euthanasia at four distinct time intervals (7, 14, 21, and 28) days. Biochemical analyses were done. Teriparatide was shown to elevate serum levels of bone alkaline phosphatase (BALP), elevate serum calcium concentration levels, and lower serum phosphate. There were statistically significant differences in the levels of BALP between the control group and the treated group at 7, 14, and 21 days after the surgical procedure and there was a statistically significant difference in serum calcium levels between the treated group and the control group on day 14 of the experiment. The findings of this research suggest that the systemic administration of teriparatide resulted in an acceleration of bone healing. This was evidenced by a notable elevation in bone alkaline phosphatase levels as seen in the biochemical analysis. Teriparatide slightly elevated serum calcium levels and lowered serum phosphate levels because it is a synthetic parathyroid hormone.

Summary Post‐traumatic lipid inclusion cysts are a rare entity seen following fractures in paediatric patients. They often occur in the distal radius, developing 1–3 months following an extra‐articular fracture. Although benign and self‐limiting in nature, adequate awareness and accurate radiographic interpretation is key in avoiding further unnecessary non‐invasive or invasive investigations. We report on a case of post‐traumatic lipid inclusion cyst and review the literature. [ABSTRACT FROM AUTHOR]

Objectives: Chronic kidney disease (CKD) complicated by secondary hyperparathyroidism (SHPT) is associated with an increased risk of fragility fractures. Etelcalcetide (EC) is a treatment for SHPT that reduces serum parathyroid hormone (PTH) levels. However, the effects of combined treatment with osteoporosis drugs such as teriparatide (TPTD) remain unclear. This study investigates the combined effects of EC and TPTD on bone in CKD model rats. Methods: The CKD model was established in 8-week-old male Wistar rats by feeding them a 0.75% adenine diet for 4 weeks. At 20 weeks of age, the rats were divided into 4 groups (N = 9–10 in each group): CKD group (vehicle administration), TPTD group (30 μg/kg, 3 times/week), EC group (0.6 mg/kg, daily), and Comb group (TPTD and EC combined). EC was injected for 12 weeks starting at 20 weeks of age, and TPTD was injected for 8 weeks starting at 24 weeks of age. After treatment, the followings were evaluated: bone mineral density, bone strength, biochemical tests, bone and fat histomorphometry, and micro-computed tomography. Results: In CKD model rats, the combination of EC and TPTD was more effective in increasing cortical bone thickness and bone strength and inhibiting porosity. In addition, the combined treatment decreased bone marrow adiposity and fibrosis, and it increased bone mass and improved bone microstructure in trabecular bone. Conclusions: With the observed benefits such as improved bone mass, bone strength, structural properties, and bone marrow adiposity, combination therapy may be a potential way to improve bone fragility in CKD.

Objective Romosozumab is increasingly employed to manage osteoporosis. However, no studies have analyzed its effects on recent osteoporotic vertebral compression fractures (OVCFs). Therefore, this study aimed to evaluate the efficacy of romosozumab compared with teriparatide in managing OVCFs. Methods The electronic medical records of postmenopausal patients with recent OVCFs who were administered romosozumab or teriparatide for one year from March 2018 to August 2022 were retrospectively reviewed. We compared the 2 groups for demographics, radiological outcomes (compression ratio, Cobb angle, and bone mineral density [BMD]), and clinical outcomes (Numerical Rating Scale [NRS] for back pain). Results Fifty-five patients with OVCFs, 32 patients treated with romosozumab and 23 with teriparatide, were included in this study. The change of BMD (g/cm2) values was significantly higher (p = 0.016) in the romosozumab (0.04 ± 0.06) than in the teriparatide group (0.00 ± 0.08) in the femur total. Furthermore, in subgroup analysis, the change of BMD (g/cm2) values in the lumbar spine was significantly higher (p = 0.016) in the romosozumab (0.12 ± 0.06) than in the teriparatide group (0.07 ± 0.06) in the lumbar spine. The decrease in NRS was significantly higher (p = 0.013) in the romosozumab (6.6 ± 2.0) than in the teriparatide group (5.5 ± 2.1). However, there was no significant difference in radiologic outcomes between the 2 groups. Conclusion Our findings suggest that romosozumab may be more effective than teriparatide in treating OVCFs in postmenopausal females, particularly in improving BMD and reducing back pain as measured by NRS.

Study Design Retrospective cohort study. Purpose This study aimed to compare the efficacy of bisphosphonates and teriparatide in the management of osteoporotic vertebral compression fractures with regard to pain management, prevention of nonunion, and radiological as well as clinical outcomes. Overview of Literature Osteoporosis refers to a skeletal disorder characterized by decreased bone strength caused by poor bone density and quality causing fragility, resulting in long periods of pain-related immobilization. Methods In a 24-month follow-up retrospective study, 191 patients with osteoporotic vertebral compression fractures were randomly assigned to the bisphosphonate group (n=104) or the teriparatide group (n=87), with patients opting for their treatment between January 2016 and October 2020. Demographic data and patient-reported outcomes scores, including the Visual Analog Scale (VAS), Oswestry Disability Index (ODI), union rates, and kyphosis progression, were assessed at baseline, 6 months, 1 year, and 2 years after treatment. Results Both groups had a significant decrease in VAS, from 8.38±0.74 to 3.15±1.40 in the bisphosphonate group and from 8.49±0.73 to 1.11±0.31 in the teriparatide group. The ODI scores reduced significantly at 2-year follow-ups, recording 25.02±13.94 and 15.11±2.17 in the bisphosphonate and teriparatide groups, respectively. Risks of nonunion development were slightly higher at 11.53% in the bisphosphonate group and 8.63% in the teriparatide group required operative intervention. The kyphosis progression angles were also significantly lower in the teriparatide group (4.97°±0.78°) than in the bisphosphonate group (8.09°±1.25°). Conclusions Over time, numerous studies have demonstrated the efficacy of bisphosphonates and teriparatide in ameliorating pain. In this study, the efficacy of teriparatide surpassed that of bisphosphonates in certain aspects, such as the initial 6-month union rates and reduction in the progression of segmental kyphosis. However, bisphosphonates and teriparatide yield similar and favorable union rates at 1 year and final follow-up.

Background: Teriparatide (TPTD) is a widely used anabolic agent for the treatment of osteoporosis. Several factors have been identified to be related to bone mineral density (BMD) increase in anti-osteoporosis treatment with other agents; however, there has been no systematic analysis to summarize the associated determinants of BMD reaction to daily teriparatide treatment. Methods: In this retrospective study, we performed a comprehensive investigation involving not only clinical data but also several relevant lifestyle factors to be examined for their potential contribution to BMD response. This post-hoc analysis included 258 post-menopaused patients with osteoporosis who received TPTD at 20 µg/day for 12 months. Univariate and multivariate analyses were conducted to distinguish the response variables of lumbar spine (LS) BMD transformation, the principal outcome measure of efficacy, from the baseline at 12 months. Results: Twelve months of TPTD treatment resulted in an absolute 0.39 ± 0.37 increase in T-score of LS BMD. Gastrointestinal disease, prior bisphosphonate or glucocorticoid treatment, no vitamin K2 supplementation, low levels of serum 25(OH)D and PINP, weak increment of PINP and β-CTX at 3 months, unhealthy lifestyle (excessive smoking, tea, coffee, and drinking), vegetarian diet pattern, low ALT level, and high BMD at baseline were determined by univariate analyses to be related to the weak reaction of TPTD treatment (P < 0.10). In the multiple regression model, postmenopausal women with vitamin K2 supplementation, higher baseline serum 25(OH)D level, and higher PINP concentration at 3 months indicated a good reaction of LS BMD at 12 months (P < 0.05). Patients with gastrointestinal disease, prior bisphosphonate and glucocorticoid treatment, vegetarian diet pattern, and higher baseline BMD were significantly more likely to have a lower absolute LS BMD response compared to patients without these characteristics (P < 0.05). Further analysis confirmed the negative effect of unhealthy lifestyle on TPTD treatment. Conclusion: Our results emphasize the significance of a comprehensive assessment of clinical or lifestyle-related characteristics of postmenopausal women with osteoporosis in the management of TPTD therapy in routine care. [ABSTRACT FROM AUTHOR]

Osteoporotic vertebral compression fractures (OVCFs) are the most common osteoporotic fractures in postmenopausal women. One the other hand, they may be misdiagnosed if the deformity is not severe at the time of occurrence. In general, it is treated through absolute bed rest and braces. Vertebroplasty or kyphoplasty is sometimes performed when there is a severe decrease in the height of the vertebral body. In addition, transpedi cular fixation can be performed when there is an accompanying injury to the posterior complex or neurologic symptoms. In this case, the authors performed minimally invasive transpedicular fixation after achieving vertebral body height recovery through postural reduction in OVCF patient who were neglected for one month after the injury. After securing initial stability through screw fixation, complete bony union was achieved more quickly and stably through weekly teriparatide administration. The authors report this case with a review of the relevant literature. [ABSTRACT FROM AUTHOR]

The increased incidence of atypical femoral fractures (AFFs) appears to be related to an aging population and a consequent increase in bisphosphonate use. In patients with AFF, the bone healing potential for fracture union is generally suppressed, and the surgical techniques for internal fixation are often challenging. Therefore, complications, such as fixation failure, delayed union, and nonunion, are frequently reported. Prompt discontinuation of bone resorption inhibitors, including bisphosphonates, is fundamental to the successful treatment of AFF. In addition, calcium and vitamin D should be supplemented, and known risk factors for nonunion should be excluded. Intramedullary nailing is considered the treatment of choice in the surgical management of AFF. During surgery, anatomical reduction and the firm internal fixation of fracture fragments are required while preserving the surrounding soft tissue. There are reports on the benefits of postoperative parathyroid hormone administration in fracture healing, but more evidence is needed. [ABSTRACT FROM AUTHOR]

Background: Observational studies have shown a causal association between dyslipidemia and osteoporosis, but the genetic causation and complete mechanism of which are uncertain. The disadvantage of previous observational studies is that they are susceptible to confounding factors and bias, that makes it difficult to infer a causal link between those two diseases. Abnormal epigenetic modifications, represented by DNA methylation, are important causes of many diseases. However, there are no studies showing a bridging role for methylation modifications in blood lipid metabolism and osteoporosis. Methods: SNPs for lipid profile (Blood VLDL cholesterol (VLDL-C), blood LDL cholesterol (LDL-C), blood HDL cholesterol (HDL-C), blood triglycerides (TG), diagnosed pure hypercholesterolaemia, blood apolipoprotein B (Apo B), blood apolipoprotein A1(Apo A1)), and bone mineral density (BMD) in different body parts (Heel BMD, lumbar BMD, whole-body BMD, femoral neck BMD) were obtained from large meta-analyses of genome-wide association studies as instrumental variables for two-sample Mendelian randomization. Assessment of the genetic effects of lipid profile-associated methylation sites and bone mineral density was carried out using the summary-data-based Mendelian randomization (SMR) method. Results: Two-sample Mendelian randomization showed that there was a negative causal association between hypercholesterolaemia and heel BMD (p = 0.0103, OR = 0.4590), and total body BMD (p = 0.0002, OR = 0.2826). LDL-C had a negative causal association with heel BMD (p = 8.68E-05, OR = 0.9586). VLDL-C had a negative causal association with heel BMD (p = 0.035, OR = 0.9484), lumbar BMD (p = 0.0316, OR = 0.9356), and total body BMD (p = 0.0035, OR = 0.9484). HDL-C had a negative causal association with heel BMD (p = 1.25E-05, OR = 0.9548), lumbar BMD (p = 0.0129, OR = 0.9358), and total body BMD (p = 0.0399, OR = 0.9644). Apo B had a negative causal association with heel BMD (p = 0.0001, OR = 0.9647). Apo A1 had a negative causal association with heel BMD (p = 0.0132, OR = 0.9746) and lumbar BMD (p = 0.0058, OR = 0.9261). The p-values of all positive results corrected by the FDR method remained significant and sensitivity analysis showed that there was no horizontal pleiotropy in the results despite the heterogeneity in some results. SMR identified 3 methylation sites associated with lipid profiles in the presence of genetic effects on BMD: cg15707428(GREB1), cg16000331(SREBF2), cg14364472(NOTCH1). Conclusion: Our study provides insights into the potential causal links and co-pathogenesis between dyslipidemia and osteoporosis. The genetic effects of dyslipidaemia on osteoporosis may be related to certain aberrant methylation genetic modifications. [ABSTRACT FROM AUTHOR]

Phenylacetylglutamine (PAG), a gut microbiota metabolite, is associated with cardiovascular diseases. Arterial stiffness (AS), which is a marker of aging-associated vascular diseases, is an independent risk factor for cardiovascular morbidity and mortality. This study aimed to assess the correlation between serum PAG levels and AS in kidney transplantation (KT) patients, potentially uncovering new insights into the cardiovascular risks in this population. In this study, 100 KT patients were included. Carotid–femoral pulse wave velocity (cfPWV) was measured, and patients with cfPWV > 10 m/s were categorized as the AS group. Serum PAG levels were assessed using liquid chromatography–tandem mass spectrometry. Thirty KT patients (30.0%) exhibited AS, with higher percentages of diabetes mellitus, older age, and elevated levels of systolic blood pressure, serum fasting glucose, and PAG than the control group. After adjusting for factors significantly associated with AS by multivariate logistic regression analysis, serum PAG, age, fasting glucose levels, and systolic blood pressure were independent factors associated with AS. Furthermore, PAG levels had a negative correlation with the estimated glomerular filtration rate and a positive correlation with cfPWV values. Serum PAG levels are positively associated with cfPWV values and are a biomarker of AS in KT patients. [ABSTRACT FROM AUTHOR]

To assess the correlation between serum fibroblast growth factor 23 (FGF-23)/Klotho levels and end-stage renal disease (ESRD) in middle-aged and elderly patients combined with low bone mineral density (BMD). The BMD of the lumbar vertebrae and femoral neck of 87 patients with ESRD was measured using a dual-energy X-ray bone densitometer during hospitalisation and the patients were divided into a normal bone mass group and a low bone mass group. Haemoglobin, albumin, urea nitrogen, uric acid, creatinine, low-density lipoprotein cholesterol, alkaline phosphatase, blood calcium, blood phosphorus and full parathyroid hormone were detected using an automatic biochemical analyser. The levels of serum FGF-23, Klotho and activated vitamin D in the patients with ESRD were measured via an enzyme-linked immunosorbent assay. Older age and decreased serum creatinine levels and serum Klotho levels were associated with low bone mass. There were significantly more men in normal bone mass group (n=49, 74.24%) than in low bone mass group (n=8, 38.10%). The correlation analysis showed that BMD was negatively correlated with age but positively correlated with serum Klotho. The binary logistic regression analysis indicated that old age and the decrease in serum Klotho level were independent risk factors of a low BMD (all p<0.05). In conclusion, serum Klotho is closely related to BMD changes in middle-aged and elderly patients with ESRD. A high Klotho level is a protective factor and is expected to be a marker in reducing bone mineral metabolism disorders and improving the prognosis of patients with ESRD. [ABSTRACT FROM AUTHOR]

Senile osteoporosis increases fracture risks. Bone marrow stromal cells (BMSCs) are sensitive to aging. Deep insights into BMSCs aging are vital to elucidate the mechanisms underlying age-related bone loss. Recent advances showed that osteoporosis is associated with aberrant DNA methylation of many susceptible genes. Galectin-1 (Gal-1) has been proposed as a mediator of BMSCs functions. In our previous study, we showed that Gal-1 was downregulated in aged BMSCs and global deletion of Gal-1 in mice caused bone loss via impaired osteogenesis potential of BMSCs. Gal-1 promoter is featured by CpG islands. However, there are no reports concerning the DNA methylation status in Gal-1 promoter during osteoporosis. In the current study, we sought to investigate the role of DNA methylation in Gal-1 downregulation in aged BMSCs. The potential for anti-bone loss therapy based on modulating DNA methylation is explored. Our results showed that Dnmt3b-mediated Gal-1 promoter DNA hypermethylation plays an important role in Gal-1 downregulation in aged BMSCs, which inhibited β-catenin binding on Gal-1 promoter. Bone loss of aged mice was alleviated in response to in vivo deletion of Dnmt3b from BMSCs. Finally, when bone marrow of young wild-type (WT) mice or young Dnmt3bPrx1-Cre mice was transplanted into aged WT mice, Gal-1 level in serum and trabecular bone mass were elevated in recipient aged WT mice. Our study will benefit for deeper insights into the regulation mechanisms of Gal-1 expression in BMSCs during osteoporosis development, and for the discovery of new therapeutic targets for osteoporosis via modulating DNA methylation status. NEW & NOTEWORTHY There is Dnmt3b-mediated DNA methylation in Gal-1 promoter in aged bone marrow stromal cell (BMSC). DNA methylation causes Gal-1 downregulation and osteogenesis attenuation of aged BMSC. DNA methylation blocks β-catenin binding on Gal-1 promoter. Bone loss of aged mice is alleviated by in vivo deletion of Dnmt3b from BMSC. [ABSTRACT FROM AUTHOR]

Background: With the increasing life expectancy of people living with HIV (PLWH) following antiretroviral therapy (ART), there is a growing prevalence of chronic diseases such as osteonecrosis of the femoral head (ONFH). Compared with the more accessible blood, the viral infection profile in bone marrow and necrotic femoral heads in PLWH remains inadequately characterized. Methods: Femoral head and bone marrow were collected from 15 PLWH undergoing total hip arthroplasty. For each femoral head, samples were obtained from the subchondral, necrotic, sclerotic, and normal areas. HIV DNA and HIV RNA assays were employed to evaluate disparities in viral load and reservoir between bone marrow and blood, as well as to quantify viral infection in distinct regions of the necrotic femoral head. Results: Blood HIV RNA dropped below detectable levels in 8 patients (below 20 copies/mL). The median of bone marrow HIV RNA was 255.89 copies/mL. HIV DNA in blood and bone marrow was 296.35 and 454.31 copies/106 cells. HIV DNA in necrotic area was about half that in sclerotic area, HIV RNA was about twice that in normal area, the difference was statistically significant. Conclusion: Despite using ART, there is still substantial active HIV and a potential reservoir in the bone marrow. Viral transcription was most active in the necrotic area of the femoral head, which may indicate that HIV itself is directly involved in ONFH. [ABSTRACT FROM AUTHOR]

The intermittent injection of teriparatide, a recombinant fragment of human parathyroid hormone (PTH 1–34), activates anabolic activity on bone turnover. However, the PTH administration period is limited to 2 years. Thus, sequential therapy after discontinuation of PTH is required. Low‐intensity pulsed ultrasound (LIPUS) has been widely used for bone fracture healing. In this study, we examined the effects of LIPUS on bone mass after PTH withdrawal in ovariectomized (OVX) model mice. The LIPUS‐non‐irradiated femoral trabecular bone mineral density (BMD) in the treated after PTH withdrawal was significantly decreased. Meanwhile, the femoral BMD in the OVX + PTH‐LIPUS group was remarkably higher than that of the OVX group. Additionally, mRNA expression of Runx2, Osterix, Col1a1, and ALP increased significantly following LIPUS irradiation after PTH withdrawal. These results suggest that LIPUS protected against femoral trabecular BMD loss and up‐regulated the osteogenic factors following PTH withdrawal in OVX mice. [ABSTRACT FROM AUTHOR]

Prolonged inactivity and disuse conditions, such as those experienced during spaceflight and prolonged bedrest, are frequently accompanied by detrimental effects on the motor system, including skeletal muscle atrophy and bone loss, which greatly increase the risk of osteoporosis and fractures. Moreover, the decrease in glucose and lipid utilization in skeletal muscles, a consequence of muscle atrophy, also contributes to the development of metabolic syndrome. Clarifying the mechanisms involved in disuse-induced musculoskeletal deterioration is important, providing therapeutic targets and a scientific foundation for the treatment of musculoskeletal disorders under disuse conditions. Skeletal muscle, as a powerful endocrine organ, participates in the regulation of physiological and biochemical functions of local or distal tissues and organs, including itself, in endocrine, autocrine, or paracrine manners. As a motor organ adjacent to muscle, bone tissue exhibits a relative lag in degenerative changes compared to skeletal muscle under disuse conditions. Based on this phenomenon, roles and mechanisms involved in the communication between skeletal muscle and bone, especially from muscle to bone, under disuse conditions have attracted widespread attention. In this review, we summarize the roles and regulatory mechanisms of muscle-derived myokines and extracellular vesicles (EVs) in the occurrence of muscle atrophy and bone loss under disuse conditions, as well as discuss future perspectives based on existing research. [ABSTRACT FROM AUTHOR]

Background: Patients with depression, especially women, are associated with low bone mineral density (BMD). Traditional antidepressants are associated with negative effects on BMD. Few studies have examined the effect of ketamine on BMD, and it remains unclear whether there are sex differences in the effects of ketamine on BMD in patients with depression. Methods: A total of 102 patients with unipolar and bipolar depression were administered six infusions of intravenous ketamine over a 12-day period. Plasma levels of eight bone markers were examined at baseline, 24 h after the sixth infusion and again 2 weeks (Days 13 and 26). Results: Linear mixed models showed all bone markers had significant time main effect (all p < 0.05). Compared with baseline, the whole sample showed increased levels of leptin and osteoprotegerin at Days 13 and 26, as well as Dickkopf-related protein 1 at Day 13, and decreased levels of osteocalcin, sclerostin, osteopontin, parathyroid hormone and fibroblast growth factor 23 at Days 13 and 26 (all p < 0.05). Females had a higher level of leptin at Days 13 and 26, and lower levels of osteocalcin and sclerostin at Day 13 than males (all p < 0.05). Increases of leptin were associated with depressive symptom improvements at Day 13 and Day 26 in females (both p < 0.05). In males, higher baseline osteocalcin levels were associated with greater depressive symptom improvement at Day 26 (β = 0.414, p = 0.009). Conclusions: Our results suggest that repeated ketamine infusions may be associated with modulation of bone markers in patients with depression and present sex differences. Baseline osteocalcin level may be served as a predictor for the antidepressant effects of ketamine in males. Trial registration Data were derived from an open label clinical trial, which was registered at Chinese Clinical Trial Registry (ChiCTR-OOC-17012239). Registered 26 May 2017. http://www.chictr.org.cn Plain language summary: Depression and low bone mineral density (BMD) are epidemiologically linked and traditional antidepressants may act as a risk factor for BMD. However, it is unclear whether the novel antidepressant, ketamine, has effects on bone markers in patients with depression and whether there are sex differences on these effects. Ketamine infusions may be associated with modulation of bone markers and may exert a positive effect on BMD in patients with depression, which present sex differences. The study results may inform potential strategies for prevention of low BMD during the treatment of depression. Clinicians should be aware of the bone markers because some of them may be associated antidepressant response. Highlights: Depression is usually associated with low bone mineral density (BMD) and traditional antidepressants have negative effects on BMD. Ketamine, as a novel antidepressant, modulated multiple bone markers and might exert a positive effect on BMD in patients with depression, which present sex differences. Increases of leptin were positively associated with depressive symptom improvements in females across six ketamine infusions. Baseline osteocalcin level may be served as a predictor for the antidepressant effects of ketamine in males. [ABSTRACT FROM AUTHOR]

Background: Atypical femur fractures are a rare occurrence, especially in bisphosphonate-naïve men, and merit reporting owing to their unusual presentation and clinical implications. This case report highlights a unique instance of atypical femur fractures in a 73-year-old male with no prior bisphosphonate exposure. Case presentation: The patient, a 73-year-old Indian male with no history of bisphosphonate use, presented with left thigh pain and swelling following a minor fall. Radiographic assessment unveiled a closed left mid diaphyseal femoral shaft fracture. Subsequent imaging revealed an impending fracture in the contralateral femur. A comprehensive diagnostic evaluation, encompassing radiographic analysis, laboratory tests, and clinical assessment confirmed the diagnosis. Surgical management via intramedullary nailing was pursued for both fractures. Notably, the patient's medical history was characterized by radiographic manifestations, the infrequent occurrence of atypical femur fractures in men, and associated risk factors. Treatment encompassed anabolic bone therapy employing teriparatide, alongside discontinuation of antiresorptive agents. Conclusions: This case underscores the significance of considering atypical femur fractures in older individuals with limited trauma history. It accentuates the role of anabolic agents in the therapeutic regimen and contributes to the evolving understanding of atypical femur fractures. The report underscores the need for vigilant monitoring and tailored management strategies in similar cases, thereby enhancing clinical practice and patient care. [ABSTRACT FROM AUTHOR]

Background: The therapeutic efficacy of renin-angiotensin system inhibitors (RASi) in elderly patients with hypertension and at risk of fractures has been in the limelight because of accumulating evidence that localized RAS activation in bone tissue leads to osteoclastic bone resorption, resulting in osteoporosis. This study set out to investigate the association between RASi use and fracture incidence in a large cohort. Methods: We employed a nested case–control design to investigate the association between RASi use and newly developed fractures. A case was defined as a patient newly diagnosed with a fracture between January 2004 and December 2015. We selected 1,049 cases and controls using 1:1 propensity score matching. Conditional logistic regression analysis was conducted to estimate the association between RASi exposure and fracture incidence. Results: Overall, RASi usage was significantly associated with lower odds for fracture incidence (ever-users vs never-users: OR, 0.73; 95% CI, 0.59–0.91). We found that ARB-only users experienced fewer fractures than RASi-never users (OR, 0.65; 95% CI, 0.49–0.86), whereas ACEi-only users or ARB/ACEi-ever users did not. In subgroup analysis, RASi-ever users without cerebrovascular disease, those with a BMI exceeding 23, and statin exposure had significantly lower ORs. Conclusions: The present study established a significant association between RASi use and reduced fracture incidence, thus highlighting the potential clinical utility of RASi use as a preventive strategy in elderly patients at risk for osteoporotic fractures. [ABSTRACT FROM AUTHOR]

Background: This research was conducted to create a treatment for osteoporosis (bone degenerating disorder) with hormone replacement therapy using Hydroxyapatites and chitosan as a composite. The research aims to develop bio-composite hydroxyapatite/chitosan-drug composites that will improve the absorption of calcium and phosphorus ions into the bone by acting as an extra source of these nutrients. Hydroxyapatite which resembles to bone minerals composition was prepared using chemical reaction method later incorporating it with chitosan using co-precipitation method forming hydroxyapatite-chitosan composites. Materials and Methods: Finally synthesizing Hydroxyapatite/Chitosan-Drug composite using homogenous mixture kept for 12 hr for incorporation. The prepared Hydroxyapatite and hydroxyapatite/chitosan composites underwent XRD, FTIR and TGA studies giving us sharp diffraction peaks, functional group characteristic peaks and percentage weight loss respectively. Results and Discussion: Micrometrics measurements of the composites of hydroxyapatite and chitosan reveal good, Carr's index, percentage porosity and Hausner's ratio in batch F5 and F6 out of all six batches. HA/CS composites were also evaluated for water absorption study, water loss study, estimation of calcium and phosphorous ion. Estimation of phytogenic steroid and in-vitro drug release study was done on HA/CS-drug composites. Conclusion: As a conclusion, AFM study of batch F5 with drug revealed there was an improvement in uniformity of composite size and shape. The X drug was able to homogeneously incorporate in HA/CS composites giving good release of drug up to 12 hr. The study produced nano-composites, an innovative bone regeneration and tissue creation approach. [ABSTRACT FROM AUTHOR]

Objectives: Atypical femoral fracture (AFF) is an atypical low-energy subtrochanteric and diaphyseal femoral fracture. Even if bone fusion is achieved in patients with AFF, the risk of AFF in the contralateral femur must be considered. This study aimed to investigate the factors affecting complete AFF in the contralateral femur and conservatively treated incomplete AFF. Subject and Methods: Radiographs of 111 femurs in 104 AFF cases were examined, and the femurs were classified as follows: 85 contralateral femurs with complete AFF; 18 contralateral femurs with incomplete AFF; 8 femurs with incomplete AFF without surgical treatment. Various patients' clinical data were collected, and we investigated the factors affecting the second complete AFF. Results: Complete fractures occurred in 10 (9.7%) of 103 femurs without incomplete AFF at the first visit and in 3 (37.5%) of 8 femurs with incomplete AFF. The Kaplan-Meier curve revealed that lateral cortical bone thickening and thigh pain were associated with significantly poorer prognoses (p = 0.026 and p = 0.013, respectively). Multivariate analyses revealed that eldecalcitol usage after AFF onset (p = 0.0094) and previous use of bisphosphonate or denosumab (p = 0.0126) were protective factors for second complete AFF and that the presence of thigh pain (p = 0.0134) was a risk factor for second complete AFF. Conclusions: Eldecalcitol administration after bone union of first AFF may prevent AFF recurrence. In addition, painful incomplete AFF has a high risk of developing a complete fracture. [ABSTRACT FROM AUTHOR]

Summary: Evidence on the management of rebound-associated vertebral fractures after denosumab discontinuation is scarce. This study describes seven patients retreated with denosumab, teriparatide or zoledronate for 24 months. Their bone mineral density remained stable or improved and no new fractures occurred suggesting that all three options might be adequate for their treatment. Purpose: To describe the densitometric and biochemical changes achieved with osteoactive treatment after 24 months of follow-up in patients who suffered rebound-associated vertebral fractures (RAVFs) after Dmab discontinuation, and to report the occurrence of new vertebral and non-vertebral fractures. Methods: Patients with RAVFs who received retreatment (RT) for 24 months were included. Bone mineral density (BMD) was assessed by dual-energy x-ray absorptiometry at the lumbar spine (LS), femoral neck (FN) and total hip (TH), along with C-terminal cross-linked telopeptide of type I collagen, osteocalcin, and bone alkaline phosphatase. Data were collected at the start of the RT and after 24 months. Results: Seven female patients were included. RT consisted in Dmab (n = 3), teriparatide (TPT) (n = 3) and zoledronate (Zol) (n = 1). At 24 months, the mean BMD change was 2.2% at LS, 6.8% at FN and 3.8% at TH in the Dmab group, 7.5% at LS, 1.4% at FN and 3.7% at TH in the TPT group and, 5.0% at LS, 0.6% at FN and 3.9% at TH in the patient with Zol. After 24 months of follow-up, no patient suffered new fractures. Conclusion: In this series of patients with RAVFs, we did not observe any new fractures and the BMD remained stable after 24 months of RT. Future studies are needed to evaluate the most suitable treatment approach after RAVFs but these preliminary data suggest that all denosumab, zoledronate and teriparatide might be adequate options. [ABSTRACT FROM AUTHOR]

Introduction: Previous research has confirmed that patients with type 2 diabetes mellitus tend to have higher bone mineral density (BMD), but it is unknown whether this pattern holds true for individuals without diabetes. This Mendelian randomization (MR) study aims to investigate the potential causal relationship between various glycemic trait (including fasting glucose, fasting insulin, 2-h postprandial glucose, and glycated hemoglobin) and BMD in non-diabetic individuals. The investigation focuses on different age groups (15–30, 30–45, 45–60, and 60 + years) and various skeletal sites (forearm, lumbar spine, and hip). Materials and methods: We utilized genome-wide association study data from large population-based cohorts to identify robust instrumental variables for each glycemic traits parameter. Our primary analysis employed the inverse-variance weighted method, with sensitivity analyses conducted using MR-Egger, weighted median, MR-PRESSO, and multivariable MR methods to assess the robustness and potential horizontal pleiotropy of the study results. Results: Fasting insulin showed a negative modulating relationship on both lumbar spine and forearm. However, these associations were only nominally significant. No significant causal association was observed between blood glucose traits and BMD across the different age groups. The direction of fasting insulin's causal effects on BMD showed inconsistency between genders, with potentially decreased BMD in women with high fasting insulin levels and an increasing trend in BMD in men. Conclusions: In the non-diabetic population, currently available evidence does not support a causal relationship between glycemic traits and BMD. However, further investigation is warranted considering the observed gender differences. [ABSTRACT FROM AUTHOR]

Introduction: we report the emergence of resistance to the action of teriparatide in a patient with postsurgical hypoparathyroidism under replacement therapy with this molecule, who initially showed an optimal response. Case report: description of a case report in which a patient with postsurgical hypoparathyroidism treated with teriparatide showed progressive decrease in its effectiveness, and resistance to the biosimilar teriparatide with which the patient was treated was tested. The Ellsworth-Howard test was used to evaluate teriparatide resistance. Discussion: the patient showed a response to the Ellsworth-Howard test consistent with resistance to teriparatide. A comparison was made with a patient with chronic hypoparathyroidism who underwent the same test with the same molecule, obtaining an appropriate functional response. The occurrence of primary failure to teriparatide replacement therapy in the context of chronic hypoparathyroidism is presented. Autoimmune etiology due to the development of blocking autoantibodies is the most likely hypothesis. [ABSTRACT FROM AUTHOR]

Bisphosphonates are therapeutic agents that have been used for almost five decades in the treatment of various bone diseases, such as osteoporosis, Paget disease and prevention of osseous complications in cancer patients. In nuclear medicine, simple bisphosphonates such as 99mTc-radiolabelled oxidronate and medronate remain first-line bone scintigraphic imaging agents for both oncology and non-oncology indications. In line with the growing interest in theranostic molecules, bifunctional bisphosphonates bearing a chelating moiety capable of complexing a variety of radiometals were designed. Among them, DOTA-conjugated zoledronate (DOTAZOL) emerged as an ideal derivative for both PET imaging (when radiolabeled with 68Ga) and management of bone metastases from various types of cancer (when radiolabeled with 177Lu). In this context, this report provides an overview of the main medicinal chemistry aspects concerning bisphosphonates, discussing their roles in molecular oncology imaging and targeted radionuclide therapy with a particular focus on bifunctional bisphosphonates. Particular attention is also paid to the development of DOTAZOL, with emphasis on the radiochemistry and quality control aspects of its preparation, before outlining the preclinical and clinical data obtained so far with this radiopharmaceutical candidate. [ABSTRACT FROM AUTHOR]

The economic development of tight carbonate reservoirs requires hydraulic or acid fracturing stimulation. Acid fracturing better activates natural fractures, resulting in increased stimulated reservoir volume and improving oil and gas flowability. In order to solve the problem of excessive acid-rock reaction due to high temperature, this paper screened four kinds of solid forms of acid with the maximum quantity of acid and reaction rate as the index and formed a high temperature-resistant mixed solid acid system with solid organic acid as the main part and inorganic solid acid as the auxiliary part. The maximum quantity of acid produced and effective acid concentration of the system were greater than 50%, and no residue was precipitated after the complete reaction. Dynamic acid-rock rate tests were performed on different types of retarded acid at 140 °C. The test results show that the solid acid dissolves to form a low-viscosity acid solution, and the reaction rate is one order of magnitude lower than that of gelled and cross-linked acids at the same hydrogen ion concentration, and it is little affected by temperature. Moreover, the paper compares the treatment effect of micro-proppants and solid acids on micro-fractures. The results show that the core permeability improvement multiples up to 900 times under low dissolution of solid acid and the formation of oil and gas flow channels with the same scale as micro-proppants. The experimental results demonstrated the ability of solid delayed acid to transport the fracture leading edge at high temperatures and effectively activate micro-fractures. [ABSTRACT FROM AUTHOR]

Osteoporosis is characterized by low bone mass, bone microarchitecture disruption, and collagen loss, leading to increased fracture risk. In the current study, collagen peptides were extracted from milkfish scales (MS) to develop potential therapeutic candidates for osteoporosis. MS was used to synthesize a crude extract of fish scales (FS), collagen liquid (COL), and hydroxyapatite powder (HA). COL samples were further categorized according to the peptide size of total COL (0.1 mg/mL), COL < 1 kDa (0.1 mg/mL), COL: 1–10 kDa (0.1 mg/mL), and COL > 10 kDa (0.1 mg/mL) to determine it. Semi‐quantitative reverse transcription polymerase chain reaction (sqRT‐PCR) and immunofluorescence labeling were used to assess the expression levels of specific mRNA and proteins in vitro. For in vivo studies, mice ovariectomy (OVX)‐induced postmenopausal osteoporosis were developed, while the sham surgery (Sham) group was treated as a control. Collagen peptides (CP) from MS inhibited osteoclast differentiation in RAW264.7 cells following an insult with nuclear factor kappa‐B ligand (RANKL). CP also enhanced osteoblast proliferation in MG‐63 cells, possibly through downregulating NFATc1 and TRAP mRNA expression and upregulating ALP and OPG mRNA levels. Furthermore, COL1 kDa also inhibited bone density loss in osteoporotic mice. Taken together, CP may reduce RANKL‐induced osteoclast activity while promoting osteoblast synthesis, and therefore may act as a potential therapeutic agent for the prevention and control of osteoporosis. [ABSTRACT FROM AUTHOR]

Introduction: Improving bone healing by various methods is one of the research areas of oral and maxillofacial surgery, as in the surgical branches dealing with hard tissue in medicine. Many methods, such as bone grafts, drugs, hormones, and tissue engineering applications, are used in bone reconstruction and rehabilitation. Moreover, improving bone healing is critical for better surgical outcomes. This study aimed to compare early and late period effects of intermittent teriparatide application on bone graft and local simvastatin application from histopathological, histomorphometric analysis, and biochemical aspects. Materials and Methods: 24 New Zealand rabbits were divided into four groups. While experimental groups received intermittent teriparatide (30µg/kg), control groups were given sterile distilled water. A total of 3 defects were created on each rabbit's right and left tibia. Bone graft and local simvastatin were randomly applied to the opened defects, and one defect was left blank for control purposes. Rabbits were sacrificed on days 15 and 30 to examine early and late bone healing. Blood was drawn for biochemical analysis. Results: The healing score and new bone development in teriparatide applied and grafted defects were statistically significant compared to all groups (p<0.05). A statistically significant difference was obtained in grafted defects compared to the control group in teriparatide-applied defects. Local simvastatin caused necrosis in both experimental and control groups. Teriparatide administration does not cause a statistically significant change in calcium, potassium, and parathyroid hormone biomarkers (p>0.05). Conclusion: Better bone healing and bone graft healing in rabbits treated with teriparatide may encourage improved surgical outcomes in clinical practice. [ABSTRACT FROM AUTHOR]

Trauma, tooth loss, cancer surgery, congenital malformations, periodontal disease, and oral-maxillofacial surgery are all major causes of bone loss, deformity, or fracture. Bone healing is a physiologically complicated process that also incorporates mechanical factors. Too many doubts concerning bone regeneration and the conditions that promote it have persisted for far too long. To assess the impact of systemic teriparatide therapy on mandibular bone defects healing. Forty male albino rats were randomly divided into two groups: the control group and the treatment group, with 20 rats per group. All rats had the same surgical technique. A small hole was created in the mandible, measuring 3 mm in diameter and 3 mm in depth, and then left unoccupied. The treatment group received a daily subcutaneous injection of Teriparatide at a dose of 10 µg/kg. Animals were subjected to euthanasia at four distinct time intervals (7, 14, 21, and 28) days. Biochemical analyses were done. Teriparatide was shown to elevate serum levels of bone alkaline phosphatase (BALP), elevate serum calcium concentration levels, and lower serum phosphate. There were statistically significant differences in the levels of BALP between the control group and the treated group at 7, 14, and 21 days after the surgical procedure and there was a statistically significant difference in serum calcium levels between the treated group and the control group on day 14 of the experiment. The findings of this research suggest that the systemic administration of teriparatide resulted in an acceleration of bone healing. This was evidenced by a notable elevation in bone alkaline phosphatase levels as seen in the biochemical analysis. Teriparatide slightly elevated serum calcium levels and lowered serum phosphate levels because it is a synthetic parathyroid hormone. [ABSTRACT FROM AUTHOR]

Background: Participants with prediabetes are at a high risk of developing type 2 diabetes (T2D). Recent studies have suggested that blocking the receptor activator of nuclear factor-κB ligand (RANKL) may improve glucose metabolism and delay the development of T2D. However, the effect of denosumab, a fully human monoclonal antibody that inhibits RANKL, on glycemic parameters in the prediabetes population is uncertain. We aim to examine the effect of denosumab on glucose metabolism in postmenopausal women with osteoporosis and prediabetes. Methods: This is a 12-month multicenter, open-label, randomized controlled trial involving postmenopausal women who have been diagnosed with both osteoporosis and prediabetes. Osteoporosis is defined by the World Health Organization (WHO) as a bone mineral density T score of ≤ − 2.5, as measured by dual-energy X-ray absorptiometry (DXA). Prediabetes is defined as (i) a fasting plasma glucose level of 100–125 mg/dL, (ii) a 2-hour plasma glucose level of 140–199 mg/dL, or (iii) a glycosylated hemoglobin A1c (HbA1c) level of 5.7–6.4%. A total of 346 eligible subjects will be randomly assigned in a 1:1 ratio to receive either subcutaneous denosumab 60 mg every 6 months or oral alendronate 70 mg every week for 12 months. The primary outcome is the change in HbA1c levels from baseline to 12 months. Secondary outcomes include changes in fasting and 2-hour blood glucose levels, serum insulin levels, C-peptide levels, and insulin sensitivity from baseline to 12 months, and the incidence of T2D at the end of the study. Follow-up visits will be scheduled at 3, 6, 9, and 12 months. Discussion: This study aims to provide evidence on the efficacy of denosumab on glucose metabolism in postmenopausal women with osteoporosis and prediabetes. The results derived from this clinical trial may provide insight into the potential of denosumab in preventing T2D in high-risk populations. Trial registration: This study had been registered in the Chinese Clinical Trials Registry. Registration number: ChiCTR2300070789 on April 23, 2023. https://www.chictr.org.cn. [ABSTRACT FROM AUTHOR]

Background: Iguratimod has been shown to promote bone formation and inhibit bone resorption in rheumatoid arthritis patients. We aimed to explore its effect on bone metabolism and vascular calcification (VC) in kidney transplant recipients (KTRs). Methods: A post hoc analysis was conducted among the subjects in our previous randomized clinical trial (NCT 02839941). Forty-three KTRs completing bone metabolism 52 weeks after enrollment were selected for this analysis, among whom 27 patients received VC examinations. In the iguratimod group, iguratimod (25 mg twice daily) was added adjuvant to the traditional triple regimen. At the 52-week follow-up, the following parameters were assessed: serum calcium, phosphorus, 25-hydroxyvitamin D, intact parathyroid hormone (iPTH), bone alkaline phosphatase (BALP), osteocalcin, type I collagen N-terminal peptide (NTx), type I collagen C-terminal peptide (CT x), bone mineral density (BMD) of the femoral neck and lumbar spine, coronary artery calcification (CAC) and thoracic aortic calcification (TAC). Bone metabolic and VC indices were compared between the two groups using the independent samples t test and Wilcoxon nonparametric test. Results: At 52 weeks after enrollment, the iguratimod group had lower osteocalcin (p = 0.010), BALP (p = 0.015), NTx (p = 0.007), CT x (p = 0.012), CAC (p = 0.080) and TAC scores (p = 0.036) than the control group. There was no significant difference in serum calcium, phosphorus, 25-hydroxyvitamin D, iPTH and BMD between the groups. Iguratimod could reduce bone turnover markers (BTMs) at both high and low iPTH levels. The adverse effect of iguratimod was mild and tolerable. Conclusion: Iguratimod is safe, can reduce BTMs and may could attenuate VC in the first year after KT. [ABSTRACT FROM AUTHOR]

Biologics, such as pharmaceutical peptides, have notoriously short shelf lives, insufficient for long-duration space flight missions to the Moon or Mars. To enable the sustainable presence of humans on the Moon or Mars, we must develop methods for on-site production of pharmaceutical peptides in space, a concept we call the Astropharmacy. Here, we present a proof-of-concept for the first step needed: a low-mass system for pharmaceutical production designed to be stable in space. To demonstrate feasibility, we engineered strains of the space-hardy spore-forming bacterium, Bacillus subtilis, to secrete two pharmaceutical peptides important for astronaut health: teriparatide (an anabolic agent for combating osteoporosis) and filgrastim (an effective countermeasure for radiation-induced neutropenia). We found that the secretion peptides from the walM and yoqH genes of B. subtilis worked well for secreting teriparatide and filgrastim, respectively. In consideration of the Translational Research Institute for Space Health (TRISH) challenge to produce a dose equivalent in 24 h, dried spores of our engineered strains were used to produce 1 dose equivalent of teriparatide from a 2 mL culture and 1 dose equivalent of filgrastim from 52 mL of culture in 24 h. Further optimization of strain growth conditions, expression conditions, and promoter sequences should allow for higher production rates to be achieved. These strains provide the template for future optimization efforts and address the first step in the Astropharmacy, capable of on-site production, purification, and processing of biopharmaceutical compounds in platforms amenable for use in space. [ABSTRACT FROM AUTHOR]

Objective: To investigate the association between cumulative remnant cholesterol (cumRC) and the risk of new-onset fragility fractures. Methods: This study included individuals who participated in the 2006, 2008, and 2010 Kailuan health examinations. Baseline characteristics were compared between groups according to cumRC quartiles. The incidence density was calculated, and the log-rank test was used to compare the cumulative incidence. Cox proportional hazards models were used to estimate the hazard ratio (HR) and 95% confidence interval (CI), and restricted cubic spline was used to examine the possibly non-linear relation between cumRC and the risk of fragility fractures. Additional analyses were performed with stratification by age (= or <65 years). Results: A total of 43,839 individuals were included in this study. During the median follow-up period of 10.97 years, a total of 489 fragility fractures occurred. Multivariable Cox proportional hazards regression model 3 showed that the Q1 and Q4 groups versus the Q2 group were associated with a higher HR of fragility fracture (HR 1.61, 95% CI: 1.23-2.11; HR 1.38, 95% CI: 1.06-1.81), and restricted cubic spline regression analysis showed a non-linear relationship between cumRC level and the risk of fragility fractures (POverall association < 0.001, PNon-linear association = 0.001). The association was significant in the age group <65 years but not in the age group =65 years. The sensitivity analyses were consistent with the main results. Conclusions: Both too high and too low cumRC levels were associated with a greater risk of fragility fractures, and this association was more significant in young and middle-aged people. [ABSTRACT FROM AUTHOR]

Osteoporosis is currently the most prevalent bone disorder worldwide and is characterized by low bone mineral density and an overall increased risk of fractures. To treat osteoporosis, a range of drugs targeting bone homeostasis have emerged in clinical practice, including anti-osteoclast agents such as bisphosphonates and denosumab, bone formation stimulating agents such as teriparatide, and selective oestrogen receptor modulators. However, traditional clinical medicine still faces challenges related to side effects and high costs of these types of treatments. Nanomaterials (particularly gold nanoparticles [AuNPs]), which have unique optical properties and excellent biocompatibility, have gained attention in the field of osteoporosis research. AuNPs have been found to promote osteoblast differentiation, inhibit osteoclast formation, and block the differentiation of adipose-derived stem cells, which thus is believed to be a novel and promising candidate for osteoporosis treatment. This review summarizes the advances and drawbacks of AuNPs in their synthesis and the mechanisms in bone formation and resorption in vitro and in vivo, with a focus on their size, shape, and chemical composition as relevant parameters for the treatment of osteoporosis. Additionally, several important and promising directions for future studies are also discussed, which is of great significance for prevention and treatment of osteoporosis. [ABSTRACT FROM AUTHOR]

The landscape of osteoporosis management has evolved significantly over the years, witnessing a paradigm shift from conventional therapies to the emergence of biologic agents. This chapter delves into the intricate mechanisms, potential applications, and future directions of biologic interventions in osteoporosis care. Biologic agents, with their targeted approach to bone health, have revolutionized the field by offering precision-driven strategies that address the underlying mechanisms of bone fragility. This chapter explores the mechanisms of action of various biologics, including Receptor Activator of Nuclear Factor Kappa-B Ligand (RANKL) inhibitors, monoclonal antibodies targeting sclerostin, parathyroid hormone (PTH) analogues, and cathepsin K inhibitors. It discusses their potential benefits, limitations, and safety considerations, while shedding light on the promise of combination therapies that merge biologic agents with traditional approaches. Furthermore, the chapter delves into the potential applications of biologic agents in specific patient populations, the role of biomarkers in predicting treatment responses, and the influence of emerging biological targets. It also explores the advancements in novel targets and drug delivery systems that aim to enhance treatment convenience and effectiveness. By tailoring treatments based on patient characteristics and exploring novel therapeutic targets, the chapter envisions a future of precision medicine in osteoporosis care. As research continues to evolve, the chapter anticipates a transformative impact on bone health outcomes, fracture prevention, and overall quality of life for individuals at risk of osteoporosis-related fractures. Through comprehensive insights into the mechanisms, applications, and future directions of biologic agents, this chapter offers a holistic perspective on the evolving landscape of osteoporosis management. [ABSTRACT FROM AUTHOR]

Background: Osteoporosis management often involves a sequential treatment approach to optimize patient outcomes and minimize fracture risks. This strategy is tailored to individual patient characteristics, treatment responses, and fracture risk profiles. Methods: A thorough literature review was systematically executed using prominent databases, including PubMed and EMBASE. The primary aim was to identify original articles and clinical trials evaluating the effectiveness of sequential therapy with anti-osteoporosis drugs, focusing on the period from 1995 to 2023. The analysis encompassed an in-depth examination of osteoporosis drugs, delineating their mechanisms of action, side effects, and current trends as elucidated in the literature. Results and Discussion: Our study yielded noteworthy insights into the optimal sequencing of pharmacologic agents for the long-term treatment of patients necessitating multiple drugs. Notably, the achievement of optimal improvements in bone mass is observed when commencing treatment with an anabolic medication, followed by the subsequent utilization of an antiresorptive drug. This stands in contrast to initiating therapy with a bisphosphonate, which may potentially diminish outcomes in the post-anabolic intervention period. Furthermore, it has been discerned that caution should be exercised against transitioning from denosumab to PTH homologs due to the adverse effects of heightened bone turnover and sustained weakening of bone structure. Despite the absence of fracture data substantiating the implementation of integrated anabolic/antiresorptive pharmacotherapy, the incorporation of denosumab and teriparatide presents a potential avenue worthy of consideration for individuals at a heightened vulnerability to fragility fractures. Conclusions: A judiciously implemented sequential treatment strategy in osteoporosis offers a flexible and tailored approach to address diverse clinical scenarios, optimizing fracture prevention and patient outcomes. [ABSTRACT FROM AUTHOR]

Use of glucocorticoid in various diseases including rheumatology and respiratory diseases is on the rise because of its prompt beneficial effects. This culminates in osteoporosis and fragility fractures. Judicious use of glucocorticoid hence calls for attention with regard to the dose schedule, route of administration and accompanying enhancing factors. Institution of proper therapeutic management as per WHO risk stratification with anabolic and/or resorptive drugs like bisphosphonates, teriparatide or denosumab is necessary to prevent the eventuality of fragility fractures. Even otherwise, knowledge of glucocorticoid, its metabolism, various dose schedules, adverse effects are areas worth discussing. [ABSTRACT FROM AUTHOR]

Background: Osteoporosis, also called the silent disease, affects the elderly with a significant contribution to their morbidity and mortality through fragility fractures. Most nations have developed their own guidelines on managing this condition. Clinical Practice Guidelines (CPGs) are the highest quality evidence documents on a particular topic prepared by expert panels. CPGs offer standardised recommendations on a particular topic. Methods: We looked at the CPGs of nations in the last five years and present the results of this review here. This review is divided into Risk assessment, prevention, diagnosis, Non pharmacological and pharmacological management with information from major CPGs only. Results: Most CPGs agree on the broad principles of assessment , core risk factors, prevention and management with some finer differences in subtle aspects of assessment and management. There are differences in the use of screening tools based on the population numbers and affordability between nations. FRAX has been advocated for the screening with or without DEXA. Most CPGs use DEXA for confirmation of diagnosis. Intervention is based on FRAX scoring. Intervention thresholds vary. We discuss non-pharmacological management included diet and nutrition, calcium and Vitamin D, Exercise and physiotherapy, lifestyle changes and falls prevention. Pharmacological management included aspects of using different medications and their indications. The key agents recommended include Bisphosphonates, Teriparatide, Denosumab, SERMs, Hormone Replacement Therapy, and other agents including any drug holidays and duration of therapy. Conclusions: This review identified some key recommendations from CPGs from multiple nations in each of the above given aspects of osteoporosis. [ABSTRACT FROM AUTHOR]

Introduction: Osteoporosis is a disorder characterized by decreased bone mass and skeletal fragility with increased fracture risk. Chronic kidney disease presents with wide range of bone metabolic disorders, including osteoporosis. Osteoporosis prevalence is high in early stages of CKD; whereas in late stages, it coexists with renal osteodystrophy. Risk factors: Risk factors for osteoporosis include advancing age, low bone mineral density (BMD), glucocorticoid therapy, smoking, alcohol intake, etc. Diagnosis: The diagnosis of osteoporosis in renal disease is made after assessment of BMD, in addition to exclusion of chronic kidney disease–mineral bone disorder (CKD–MBD), eliciting history of prior fragility fractures and relevant laboratory investigations. Management: The treatment of osteoporosis varies with the different stages of CKD, with management in stages 1–3 being similar to the general population. Special emphasis must be laid on prevention of fractures as well. [ABSTRACT FROM AUTHOR]

We aim was to present a case of severe osteoporosis with concern to an adult female who was under specific medication against the condition while she experienced inexplicable weight loss in association with an incidental fracture inconsistent with DXA changes. Challenges of the case management and decision making are further on explained. Real-life-medicine poses multiple issues that require an individual decision while respecting the standard protocols. That is why a generalized decision is rather impractical. Here we introduce the clinical case of a lady in her late 60s with a known 6-year history of osteoporosis that required several difficult decisions along surveillance: at first, zoledronic acid represented an available solution, yet after one year, BMD decreased and adjustment was done by initiating a second sequence according to the teriparatide protocol. DXA-BMD, as well as the spectrum of bone turnover markers, qualified the patient as responsive and she further continued with oral bisphosphonates while being monitored via telemedicine amid COVID-19 pandemic. After 24 more months, a second decision of zoledronic acid was done, despite prior partial response, but digestive complains restricted the oral administration of anti-osteoporotic drugs. After one more year, denosumab was initiated and consecutive follow-up is essential. At this point, another challenging aspect was revealed: the discordance between DXA - based scores increase and the presence of an incidental fracture. A supplementary investigation was considered useful (Tc-whole body scintigraphy) noting the clinical presentation with local pain, dysfunctionality, and mild weight loss that also required rehabilitation management. [ABSTRACT FROM AUTHOR]