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We aim to evaluate the Osteopontin (OPN) levels in patients with Celiac disease (CD) at diagnosis and exploring its association with mucosal atrophy and osteoporosis. The study included celiac patients at diagnosis and age and sex matched healthy controls. Subjects with additional intestinal pathology, other known inflammatory and autoimmune disease accompanying CD, and patients with signs of infection were excluded. Demographics, presenting symptoms, concurrent disorders, physical examination findings, laboratory results, celiac serology and histopathological assessment were recorded. A total of 36 celiac patients (23 girls, 13 boys, mean age 9.4 ± 4.5 years) and 36 healthy controls (22 girls, 14 boys, mean age 8.7 ± 4 years) were included. The median OPN level was significantly higher in patients [10.41 (9.34-13.47) ng/ml vs. 9.42 (7.56-10.19) ng/ml, p < 0.001]. The median OPN levels of patients with osteoporosis was significantly higher than those with normal BMD values [20.7 (10.12-21.22) vs. 9.87 (9.16-10.75), respectively, p = 0.006)]. A serum OPN level of 10.74 ng/ml was found to be a cut-off value for the patient with osteoporosis with 66.7% sensitivity, 66.7% specificity, 50% positive predictive value, and 80% negative predictive value. Patients' OPN levels were 9.53 (9.3-10.42) ng/ml in Marsh type 3a, 9.78 (8.62-15.28) ng/ml in Marsh type 3b and 11.51 (9.88-19.75) ng/ml in Marsh type 3c. Marsh-Oberhuber type 3c was found to have higher median OPN levels than type 3a and type 3b (p = 0.027). When patients were stratified based on their manifestations of either intestinal or extraintestinal symptoms, along with the presence of anemia, tissue TG IgA levels exceeding ten times the upper normal limit, and a deficiency in vitamin D, the median OPN levels exhibited no significant differences across these groups., Conclusions:  In conclusion, it is suggested that serum OPN could potentially serve as an indicator of the extent of mucosal atrophy at the initial diagnosis and may have predictive value for osteoporosis., What Is Known: • There is currently no routinely utilized marker that can ascertain the extent of histological involvement in celiac disease. • Bone mineral density evaluation is not routinely recommendable at diagnosis in celiac disease, as no clinical predictor is available for low bone mineral density in children., What Is New: • Celiac patients have a higher level of osteopontin at diagnosis. • Osteopontin could potentially serve as an indicator of the extent of mucosal atrophy at the initial diagnosis and may have predictive value for osteoporosis., Competing Interests: Declarations Ethics Approval This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of Eskisehir Osmangazi University (Date:19.03.2020/No:07). Consent to Participate Written informed consent was obtained from the parents. Competing interests The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

PCSK9 inhibitors have been shown to lower serum low density lipoprotein cholesterol (LDL-C) levels and are considered integral in the treatment of cardiovascular diseases. However, the potential association between PCSK9 inhibitors and osteoporosis is unclear now. In this study, drug-targeted mendelian randomization (MR) was utilized in conjunction with mediation analysis including bone mineral density (BMD), total 25-hydroxyvitamin D (T25(OH)D) levels and calcium supplementation to investigate the causal relationship between PCSK9 inhibitors and osteoporosis. The LDL-C level was chosen as the exposure variable in a sample size of 173,082 individuals. We conducted a MR analysis on the relationship between PCSK9 inhibitors and osteoporosis, elucidating the mediators involved. Utilizing the inverse variance weighted (IVW) method, we found the risk of osteoporosis was reduced by 0.6% in those who used PCSK9 inhibitors compared with non-users (OR: 0.994, 95%CI: 0.991-0.998, P < 0.001). In people aged 30-45 years, the risk of low BMD was 1.176 times higher among PCSK9 inhibitor users compared to non-users (OR: 1.176, 95%CI: 1.017-1.336, P = 0.045). Conversely, people aged 45-60 years who used PCSK9 inhibitors had a 14.9% lower risk of low BMD compared to non-users (OR: 0.851, 95%CI: 0.732-0.968, P = 0.007). Mediation analysis revealed that 43.33% of the impact of PCSK9 inhibitors on osteoporosis was mediated through BMD levels, with the remaining 56.67% being a direct effect. Effects of PCSK9 inhibitors on BMD levels varied in different ages. In addition, the risk of high serum T25(OH)D levels were 1.091 times among PCSK9 inhibitor users compared to non-users (OR: 1.091, 95%CI: 1.065-1.112, P < 0.001), providing valuable insights for clinicians., (© 2024. The Author(s).)

Introduction: Femoral stem subsidence is a known complication after uncemented total hip arthroplasty (THA). The purpose of this study was to determine the frequency of osteoporosis and to investigate the relationship between areal bone mineral density (aBMD) and subsidence in a cohort of patients younger than 70 years., Methods: One hundred consecutive patients (age 60 ± 6 years; 52 female, 48 male) undergoing uncemented THA using a collarless press fit femoral stem were retrospectively reviewed. Dual-energy X-ray absorptiometry (DXA) was performed preoperatively at the proximal femur and lumbar spine, and if not feasible at these sites, at the distal radius. DXA results were compared to a cohort of 100 patients ≥ 70 years scheduled for cemented THA. Age, sex, and body mass index (BMI), canal flare index (CFI), and canal fill ratio (CFR) were assessed. Analysis of stem subsidence and migration was performed on standardized, calibrated radiographs obtained postoperatively and at follow-up., Results: The frequency of osteoporosis was considerably lower in the study cohort compared to patients ≥ 70 years (7% vs. 19%, p = 0.02). Illustrated by the high CFR (mean 96 ± 4%) in the mid-stem region, a sufficient press fit was achieved. After a mean follow-up of 7.4 months, the mean stem subsidence was 0.9 ± 0.9 mm. Only two patients had subsidence greater than 3 mm, one of whom was morbidly obese and the other diagnosed with severe osteoporosis. There were no correlations between any of the parameters (CFI, CFR, age, sex, BMI) and femoral stem subsidence. In addition, aBMD T-scores showed no correlations with subsidence., Conclusion: aBMD by DXA does not appear to be associated with stem subsidence in patients younger than 70 years and with adequate press fit., (© 2023. The Author(s).)

Definition and Epidemiology: Chronic kidney disease (CKD): abnormalities of kidney structure or function, present for over 3 months. Staging of CKD is based on GFR and albuminuria (not graded). Osteoporosis: compromised bone strength (low bone mass, disturbance of microarchitecture) predisposing to fracture. By definition, osteoporosis is diagnosed if the bone mineral density T‑score is ≤ -2.5. Furthermore, osteoporosis is diagnosed if a low-trauma (inadequate trauma) fracture occurs, irrespective of the measured T‑score (not graded). The prevalence of osteoporosis, osteoporotic fractures and CKD is increasing worldwide (not graded). PATHOPHYSIOLOGY, DIAGNOSIS AND TREATMENT OF CHRONIC KIDNEY DISEASE-MINERAL AND BONE DISORDER (CKD-MBD): Definition of CKD-MBD: a systemic disorder of mineral and bone metabolism due to CKD manifested by either one or a combination of the following: abnormalities of calcium, phosphorus, PTH, or vitamin D metabolism; renal osteodystrophy; vascular calcification (not graded). Increased, normal or decreased bone turnover can be found in renal osteodystrophy (not graded). Depending on CKD stage, routine monitoring of calcium, phosphorus, alkaline phosphatase, PTH and 25-OH-vitamin D is recommended (2C). Recommendations for treatment of CKD-MBD: Avoid hypercalcemia (1C). In cases of hyperphosphatemia, lower phosphorus towards normal range (2C). Keep PTH within or slightly above normal range (2D). Vitamin D deficiency should be avoided and treated when diagnosed (1C)., Diagnosis and Risk Stratification of Osteoporosis in Ckd: Densitometry (using dual X‑ray absorptiometry, DXA): low T‑score correlates with increased fracture risk across all stages of CKD (not graded). A decrease of the T‑score by 1 unit approximately doubles the risk for osteoporotic fracture (not graded). A T-score ≥ -2.5 does not exclude osteoporosis (not graded). Bone mineral density of the lumbar spine measured by DXA can be increased and therefore should not be used for the diagnosis or monitoring of osteoporosis in the presence of aortic calcification, osteophytes or vertebral fracture (not graded). FRAX can be used to aid fracture risk estimation in all stages of CKD (1C). Bone turnover markers can be measured in individual cases to monitor treatment (2D). Bone biopsy may be considered in individual cases, especially in patients with CKD G5 (eGFR < 15 ml/min/1.73 m 2 ) or CKD 5D (dialysis)., Specific Treatment of Osteoporosis in Patients With Ckd: Hypocalcemia should be treated and serum calcium normalized before initiating osteoporosis therapy (1C). CKD G1-G2 (eGFR ≥ 60 ml/min/1.73 m 2 ): treat osteoporosis as recommended for the general population (1A). CKD G3-G5D (eGFR < 60 ml/min/1.73 m 2 to dialysis): treat CKD-MBD first before initiating osteoporosis treatment (2C). CKD G3 (eGFR 30-59 ml/min/1.73 m 2 ) with PTH within normal limits and osteoporotic fracture and/or high fracture risk according to FRAX: treat osteoporosis as recommended for the general population (2B). CKD G4-5 (eGFR < 30 ml/min/1.73 m 2 ) with osteoporotic fracture (secondary prevention): Individualized treatment of osteoporosis is recommended (2C). CKD G4-5 (eGFR < 30 ml/min/1.73 m 2 ) and high fracture risk (e.g. FRAX score > 20% for a major osteoporotic fracture or > 5% for hip fracture) but without prevalent osteoporotic fracture (primary prevention): treatment of osteoporosis may be considered and initiated individually (2D). CKD G4-5D (eGFR < 30 ml/min/1.73 m 2 to dialysis): Calcium should be measured 1-2 weeks after initiation of antiresorptive therapy (1C)., Physical Medicine and Rehabilitation: Resistance training prioritizing major muscle groups thrice weekly (1B). Aerobic exercise training for 40 min four times per week (1B). Coordination and balance exercises thrice weekly (1B). Flexibility exercise 3-7 times per week (1B)., (© 2022. The Author(s).)

Pregnancy- and lactation-associated osteoporosis (PLO) is a rare form of osteoporosis, of which the pathogenesis and best treatment options are unclear. In this report, we describe the case of a 34-year old woman diagnosed with severe osteoporosis and multiple vertebral fractures after her first pregnancy, who was subsequently treated with teriparatide (TPTD) and zoledronic acid (ZA). We describe the clinical features, imaging examination, and genetic analysis. Substantial improvements were observed in areal and volumetric bone mineral density (BMD), microarchitecture, and strength between 7 and 40 months postpartum as assessed by dual-energy X-ray absorptiometry at the total hip and spine and by high-resolution peripheral quantitative CT at the distal radius and tibiae. At the hip, spine, and distal radius, these improvements were mainly enabled by treatment with TPTD and ZA, while at the distal tibiae, physiological recovery and postpartum physiotherapy due to leg pain after stumbling may have played a major role. Additionally, the findings show that, despite the improvements, BMD, microarchitecture, and strength remained severely impaired in comparison with healthy age- and gender-matched controls at 40 months postpartum. Genetic analysis showed no monogenic cause for osteoporosis, and it is suggested that PLO in this woman could have a polygenic origin with possible susceptibility based on familiar occurrence of osteoporosis., (© 2023. The Author(s).)

Osteoporosis is a complex multifactorial disease that can lead to an increased risk of fracture. However, selective and effective osteoporosis drugs are still lacking. We showed that Asperosaponin VI (AVI) has the implications to be further developed as an alternative supplement for the prevention and treatment of bone loss. AVI has been found to have beneficial effects on metabolic diseases such as bone loss, obesity, and atherosclerosis. Our study was designed to determine the effect and mechanism of action of AVI against bone loss through regulating microbial dysbiosis. A hindlimb unloading mouse model was established to determine the effect of AVI on bone microarchitecture, gut microbiota, and serum metabolites. Eighteen female C57BL/6 J mice were divided into three groups: control, hindlimb unloading with vehicle (HLU), and hindlimb unloading treated with AVI (HLU-AVI, 200 mg/kg/day). AVI was administrated orally for 4 weeks. The results demonstrated that AVI improved the bone microstructure by reversing the decrease in bone volume fraction and trabecular number, and the increase in trabecular separation and structure model index of cancellous bone in hindlimb suspension mice. The results of 16sRNA gene sequencing suggested that the therapeutic effect of AVI on bone loss may be achieved through it regulating the gut microbiota, especially certain specific microorganisms. Combined with the analysis of ELISA, immunohistochemistry, and serum metabolome results, it could be speculated that AVI played an important role in adjusting the balance of bone metabolism by influencing specific flora such as Clostridium and its metabolites to regulate the 5-hydroxytryptophan pathway. The study explored the novel mechanism of AVI against osteoporosis, and has implications for the further development of AVI as an alternative supplement for the prevention and treatment of bone loss., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Osteoporosis is a condition of increased bone fragility associated with fractures. Apart from primary genetic osteoporotic conditions, secondary osteoporosis in children is being increasingly recognized. As a result, there is growing interest in its prevention and treatment. Important goals of care are to prevent fractures, increase bone mass and trabecular and cortical thickness, reshape vertebral fractures, prevent (or correct) skeletal deformities, and improve mobility, independence, and quality of life. Secondary pediatric osteoporosis is often of multifactorial origin since affected children frequently have more than one acquired factor that is detrimental to bone health. Typical conditions causing osteoporosis are leukemias, progressive muscle or neurological disorders, as well as chronic inflammatory conditions and their treatment. Management of children with osteoporosis involves a multidisciplinary team involving pediatric experts from different subspecialties. With regard to prevention and early intervention, it is important to provide optimal management of any underlying systemic conditions including avoidance, or dose-reduction, of osteotoxic medications. Basic supporting life-style measures, such as appropriate nutrition, including adequate calcium intake and vitamin D, and physical activity are recommended, where possible. When pediatric treatment criteria for osteoporosis are met, antiresorptive drugs constitute the first pharmacological line treatment., Conclusion: This clinical review focuses on the prevention, treatment, and follow-up of children with, or at risk of developing, osteoporosis and the transition from pediatric to adult care., What Is Known: • Osteoporosis and associated fractures can cause significant morbidity and reduce the quality of life. • The developing skeleton has huge potential for recovery and reshaping, thus early detection of fractures, assessment of recovery potential, and treatment of children with osteoporosis can prevent future fractures, deformities, and scoliosis, improve function and mobility, and reduce pain., What Is New: • Osteoporosis in children and adolescents requires a multidisciplinary approach with a thorough assessment of recovery potential, and indication for therapy should be personalized. • Although bisphosphonates still represent the drug most commonly used to increase bone mass, improve mobility, and reduce pain and recurrence of fractures, new agents are being developed and could be beneficial in children with specific conditions., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Early recognition of osteoporosis in children and adolescents is important in order to establish an appropriate diagnosis of the underlying condition and to initiate treatment if necessary. In this review, we present the diagnostic work-up, and its pitfalls, of pediatric patients suspected of osteoporosis including a careful collection of the medical and personal history, a complete physical examination, biochemical data, molecular genetics, and imaging techniques. The most recent and relevant literature has been reviewed to offer a broad overview on the topic. Genetic and acquired pediatric bone disorders are relatively common and cause substantial morbidity. In recent years, there has been significant progress in the understanding of the genetic and molecular mechanistic basis of bone fragility and in the identification of acquired causes of osteoporosis in children. Specifically, drugs that can negatively impact bone health (e.g. steroids) and immobilization related to acute and chronic diseases (e.g. Duchenne muscular dystrophy) represent major risk factors for the development of secondary osteoporosis and therefore an indication to screen for bone mineral density and vertebral fractures. Long-term studies in children chronically treated with steroids have resulted in the development of systematic approaches to diagnose and manage pediatric osteoporosis., Conclusions: Osteoporosis in children requires consultation with and/or referral to a pediatric bone specialist. This is particularly relevant since children possess the unique ability for spontaneous and medication-assisted recovery, including reshaping of vertebral fractures. As such, pediatricians have an opportunity to improve bone mass accrual and musculoskeletal health in osteoporotic children., What Is Known: • Both genetic and acquired pediatric disorders can compromise bone health and predispose to fractures early in life. • The identification of children at risk of osteoporosis is essential to make a timely diagnosis and start the treatment, if necessary., What Is New: • Pediatricians have an opportunity to improve bone mass accrual and musculoskeletal health in osteoporotic children and children at risk of osteoporosis. • We offer an extensive but concise overview about the risk factors for osteoporosis and the diagnostic work-up (and its pitfalls) of pediatric patients suspected of osteoporosis., (© 2022. The Author(s).)

Patients with anorexia nervosa (AN) often experience low bone mineral density (BMD) and increased fracture risk, with low body weight and decreased gonadal function being the strongest predictors of the observed bone mineral deficit and fractures. Other metabolic disturbances have also been linked to bone loss in this group of patients, including growth hormone resistance, low insulin-like growth factor-1 (IGF-1) concentrations, low leptin concentrations, and hypercortisolemia. However, these correlations lack definitive evidence of causality. Weight restoration and resumption of menstrual function have the strongest impact on increasing BMD. Other potential treatment options include bisphosphonates and teriparatide, supported by data from small clinical trials, but these agents are not approved for the treatment of low BMD in adolescents or premenopausal women with AN., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC part of Springer Nature.)

It has been increasingly acknowledged that bariatric surgery adversely affects skeletal health. After bariatric surgery, the extent of high-turnover bone loss is much greater than what would be expected in the absence of a severe skeletal insult. Patients also experience a significant deterioration in bone microarchitecture and strength. There is now a growing body of evidence that suggests an association between bariatric surgery and higher fracture risk. Although the mechanisms underlying the high-turnover bone loss and increase in fracture risk after bariatric surgery are not fully understood, many factors seem to be involved. The usual suspects are nutritional factors and mechanical unloading, and the roles of gut hormones, adipokines, and bone marrow adiposity should be investigated further. Roux-en-Y gastric bypass (RYGB) was once the most commonly performed bariatric procedure worldwide, but sleeve gastrectomy (SG) has now become the predominant bariatric procedure. Accumulating evidence suggests that RYGB is associated with a greater reduction in BMD, a greater increase in markers of bone turnover, and a higher risk of fracture than SG. These findings should be taken into consideration in determining the most appropriate bariatric procedure for patients, especially those at higher fracture risk. Before and after all bariatric procedures, sufficient calcium, vitamin D and protein intake, and adequate physical activity, are needed to counteract negative impacts on bone. There are no studies to date that have evaluated the effect of osteoporosis treatment on high-turnover bone loss after bariatric surgery. However, in patients with a diagnosis of osteoporosis, anti-resorptive agents may be considered., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC part of Springer Nature.)

Osteoporosis is a state of bone fragility with reduced skeletal resistance to trauma, and consequently increased risk of fracture. A wide range of conditions, including traditional risk factors, lifestyle choices, diseases and their treatments may contribute to bone fragility. It is therefore not surprising that the multi-morbid patient with chronic kidney disease (CKD) is at a particularly high risk. CKD is associated with reduced bone quantity, as well as impaired bone quality. Bone fragility in CKD is a composite of primary osteoporosis, accumulation of traditional and uremia-related risk factors, assaults brought on by systemic disease, and detrimental effects of drugs. Some risk factors are modifiable and represent potential targets for intervention. This review provides an overview of the heterogeneity of bone fragility in CKD.

Chronic kidney diseases (CKD) are associated with mineral and bone diseases (MBD), including pain, bone loss, and fractures. Bone fragility related to CKD includes the risk factors observed in osteoporosis in addition to those related to CKD, resulting in a higher risk of mortality related to fractures. Unawareness of such complications led to a poor management of fractures and a lack of preventive approaches. The current guidelines of the Kidney Disease Improving Global Outcomes (KDIGO) recommend the assessment of bone mineral density if results will impact treatment decision. In addition to bone density, circulating biomarkers of mineral, serum bone turnover markers, and imaging techniques are currently available to evaluate the fracture risk. The purpose of this review is to provide an overview of the epidemiology and pathogenesis of CKD-associated bone loss. The contribution of the current tools and other techniques in development are discussed. We here propose a current view of how to better predict bone fragility and the therapeutic options in CKD.

Bone turnover markers (BTMs) are useful parameters for assessing fracture risk and unlike bone mineral density (BMD), can be measured at any institution. However, BTM values have not been established in patients post-allogeneic hematopoietic stem cell transplantation (allo-HSCT). We investigated the practicality of BTMs in patients who underwent allo-HSCT by measuring levels of the serum bone resorption marker, tartrate-resistant acid phosphatase-5b (TRACP-5b), and the bone formation marker, bone-specific alkaline phosphatase (BAP), together with BMD, 1 month before and 6 months after allo-HSCT. Patients were classified into either the alendronate group (n = 14) if alendronate treatment (35 mg orally per week) was administered before allo-HSCT or within 1 month after allo-HSCT, or the control group (n = 16), in which patients did not receive alendronate treatment. Despite the high frequency of corticosteroids users in the alendronate group (71.4 vs. 18.9%; p < 0.01), the mean percentage changes in BMD at the lumbar spine (- 2.9 vs. - 3.1%; p = 0.44) and femoral neck (- 3.2 vs. - 4.1%; p = 1.00), TRACP-5b levels (- 4.8 vs. 9.9%; p = 0.45), and BAP levels (6.9 vs. 1.0%; p = 0.85) during 6 months did not differ significantly between the alendronate and control groups. Additionally, the percentage changes in BMD at the lumbar spine were negatively associated with the TRACP-5b levels 6 months after allo-HSCT (p = 0.03, r = 0.40). Our results indicate the possible effectiveness of alendronate treatment in allo-HSCT patients. BTM levels could be useful to monitor the BMD changes.

Sex hormone deprivation commonly occurs following menopause in women or after androgen-depletion during prostate cancer therapy in men, resulting in rapid bone turnover and loss of bone mass. There is a need to identify novel therapies to improve bone mass in these conditions. Previously, we identified age- and sex-dependent effects on bone mass in mice with deletion of the gene encoding the β-galactoside binding lectin, galectin-3 (Lgals3-KO). Due to the influence of sex on the phenotype, we tested the role of sex hormones, estrogen (β-estradiol; E 2 ), and androgen (5α-dihydroxytestosterone; DHT) in Lgals3-KO mice. To address this, we subjected male and female wild-type and Lgals3-KO mice to gonadectomy ± E 2 or DHT rescue and compared differential responses in bone mass and bone formation. Following gonadectomy, male and female Lgals3-KO mice had greater cortical bone expansion (increased total area; T.Ar) and reduced loss of bone area (B.Ar). While T.Ar and B.Ar were increased in response to DHT in wild-type mice, DHT did not alter these parameters in Lgals3-KO mice. E 2 rescue more strongly increased B.Ar in Lgals3-KO compared to wild-type female mice due to a failure of E 2 to repress the increase in T.Ar following gonadectomy. Lgals3-KO mice had more osteoblasts relative to bone surface when compared to wild-type animals in sham, gonadectomy, and E 2 rescue groups. DHT suppressed this increase. This study revealed a mechanism for the sex-dependency of the Lgals3-KO aging bone phenotype and supports targeting galectin-3 to protect against bone loss associated with decreased sex hormone production.

Osteoporosis is characterized by a bone loss associated to an increased bone marrow adiposity; however, it is still unclear what kind of lipids are involved. Therefore, the main purpose of this study was to see if there is any local bone lipid changes related to osteoporosis, by using the ovariectomy-induced osteoporosis (OVX) rat model. Female SD rats (operated at 6 months of age for skeletal maturity) were divided in control SHAM and OVX groups (n = 6/group) and maintained for 9 month post-surgery. Lipids were analyzed in two compartments of femoral diaphyses: bone marrow (BM) and mineralized tissue (MT), by chromatographic methods. As expected, osteoporotic femurs had a larger BM mass associated with a two-fold increase of lipid content. The MT had a similar lipid enrichment, indicating that adiposity affected the mineral part as well. The main lipids concerned were triglycerides, sphingomyelin, phosphatidylcholine and phosphatidylserine in BM, and triglycerides and cholesterol esters in MT. The increase of both energy-storage and membrane-associated lipids in BM suggested that cell number and/or size was enhanced to allow more triglyceride storage. Interestingly, in MT of osteoporotic femurs, sphingomyelin was decreased, suggesting that its catabolism could be linked to osteoporosis. In both femoral compartments, fatty acid profiles were enriched in 14:0 and 16:1, lowered in 18:0 and 20:4 n-6, and two-fold higher stearoyl-CoA desaturase indexes (16:1/16:0 and 18:1/18:0 ratios), suggesting an increased de novo lipogenesis in osteoporotic femurs. Thus, the present study is first to report local changes of individual lipids in rat osteoporotic femurs and suggests that osteoporosis is a pathologic condition associated with an enhanced de novo lipogenesis. Further studies will be needed to better understand the consequences of these lipid changes in osteoporotic bones.

Osteoporosis (OP) and cardiovascular diseases (CVD) are both important causes of mortality and morbidity in aging patients. There are common mechanisms underlying the regulation of bone remodeling and the development of smooth muscle calcification; a temporal relationship exists between osteoporosis and the imbalance of mineral metabolism in the vessels. Vascular calcification appears regulated by mechanisms that include both inductive and inhibitory processes. Multiple factors are implicated in both bone and vascular metabolism. Among these factors, the superfamily of tumor necrosis factor (TNF) receptors including osteoprotegerin (OPG) and its ligands has been established. OPG is a soluble decoy receptor for receptor activator of nuclear factor-kB ligand (RANKL) and TNF-related apoptosis-inducing ligand (TRAIL). OPG binds to RANKL and TRAIL, and inhibits the association with their receptors, which have been labeled as the receptor activator of NF-kB (RANK). Sustained release of OPG from vascular endothelial cells (ECs) has been demonstrated in response to inflammatory proteins and cytokines, suggesting that OPG/RANKL/RANK system plays a modulatory role in vascular injury and inflammation. For the development of potential therapeutic strategies targeting vascular calcification, critical consideration of the implications for bone metabolism must be taken into account to prevent potentially detrimental effects to bone metabolism.

Bone quality in children is generally measured with dual-energy X-ray absorptiometry (DXA). Digital X-ray radiogrammetry (DXR) uses BoneXpert to measure cortical bone quality on hand radiographs. This prospective study compared DXR and DXA results in children with high probability of secondary low bone quality, defined as DXA of the lumbar spine (DXA LS ) Z-score ≤ - 2.0. One hundred one children underwent both DXA and DXR assessment. DXA LS Z-scores were also adjusted for bone age. DXR Z-scores were compared with both DXA LS Z-scores, using Pearson correlations, Bland-Altman analysis, and sensitivity-specificity analysis. Mean bone age, DXR, and both DXA Z-scores were significantly impaired. Pearson correlation coefficients were significant between DXR Z-scores and both DXA LS Z-scores 0.507-0.564 (p < 0.001). Bland-Altman analysis showed a mean difference of 0.05-0.48 between DXR and both DXA Z-scores and showed more than 90% similarity for both DXA LS Z-scores ≤ - 2.0. DXR had a sensitivity of 67-71% and specificity of 77-83% compared to both DXA LS Z-scores.Conclusion: DXR correlates well with as well DXA LS as bone age-adjusted DXA LS Z-scores and shows good agreement with as well DXA LS as bone age-adjusted DXA LS Z-scores ≤ - 2.0. DXR shows best results when compared with DXA LS Z-scores. What is Known: • Digital X-ray radiogrammetry (DXR) may correlate well with dual-energy X-ray absorptiometry (DXA) in pediatric, adolescent, and adult patients. • DXR is a feasible method for assessment of bone quality in children. What is New: • This is the first prospective study in children with suspected secondary low bone quality that illustrates correlation between DXR and bone age-adjusted DXA Z-scores and that shows good agreement between DXR and DXA as bone age-adjusted DXA Z-scores ≤ -2.0. • Our results suggest DXR to be a good alternative for DXA for determining low bone quality.

In patients with neurofibromatosis type 1 (NF1), decreased bone mineral density (BMD) and low levels of 25-hydroxy vitamin D3 (25OHD) have been reported. Recently, the trabecular bone score (TBS) measurement has been proposed as index of bone microarchitecture and fracture risk. In 74 NF1 patients (48 females, 26 males, age 41 ± 12), we measured TBS and investigated clinical stage, lifestyle, vitamin D, serum bone turnover markers, vertebral and femoral BMD. A homogenous cohort of 61 healthy subjects was used as control group. TBS was lower in NF1 patients (1.266 ± 0.113 vs. 1.346 ± 0.105) without differences between sexes. No correlations with 25OHD, low exercise, low calcium intake, reduced sun exposure, and number of skin neurofibromas were observed. As expected, hypovitaminosis D was common (98.6%), as well as BMD reduction in hip and spine sites: In NF1 patients, bone texture evaluated by TBS was low in both sexes without any correlation with clinical or metabolic parameters, suggesting a direct role of the fibromin mutation.

Bone loss and vitamin D deficiency are common in HIV patients. However, bone health status in newly diagnosed HIV patients has not been thoroughly described. Our aim was to assess the bone mineral density (BMD), bone resorption and vitamin D status in newly diagnosed HIV patients. A prospective observational study in HIV newly diagnosed therapy-naive persons. Patients with secondary causes of osteoporosis were excluded. Bone densitometry (DXA), a bone resorption marker (CTx), 25-hydroxyvitamin D (25OHD), CD4 count and HIV viral load (VL) were done in 70 patients. Vitamin D results were compared with a group of healthy volunteers. All patients were men, mean age 31 years (19-50). Low BMD (Z score ≤ 2.0) was found in 13%, all of them in lumbar spine, and in only one patient also in femoral neck. Bone resorption was high in 16%. One out of four participants had low BMD or high bone resorption. Vitamin D deficiency (25OHD < 20 ng/mL) was found in 66%. Mean 25OHD in patients was significantly lower than in healthy volunteers (p = 0.04). No associations were found between BMD, CTx, 25OHD and VL or CD4 count. We hypothesize that HIV infection negatively affects bone health based on the results we found among newly diagnosed, therapy-naive, HIV-infected patients, without any known secondary causes of osteoporosis. Low BMD or high bone resorption, are significantly prevalent in these patients. HIV-infected patients had a higher prevalence of vitamin D deficiency than controls, which was not correlated with CD4 count or VL.

Aims: Patients with type 2 diabetes mellitus (T2DM) have an increased risk of fractures, despite having greater bone mineral density (BMD) than non-diabetic subjects. This has led to the hypothesis that the presence of impaired bone quality among diabetics reduces bone strength. The Fracture Risk Assessment Score (FRAX) algorithm, introduced to facilitate the evaluation of fracture risk, underestimates the risk of fracture in diabetic patients. The purpose of this study is to confirm the relationship between the degree of metabolic compensation and the 10-year probability of a major fracture or a hip osteoporotic fracture observed in our previous study and to ascertain whether glycosylated hemoglobin (HbA 1c ) can improve the predictive value of FRAX in patients with T2DM., Methods: Our data derive from a retrospective clinical study conducted at the "Tor Vergata" Polyclinic in Rome on 6355 subjects over 50 years of age evaluated for osteoporosis. All available clinical records were examined. HbA 1c was available for 242 of these subjects and all had had a Dual-energy X-ray Absorption (DXA) scan of the lumbar spine and femoral neck. The risk of fracture was estimated using the Italian version of the FRAX algorithm., Result: Patients with T2DM had BMD and T-scores higher than those of non-diabetic subjects, while FRAX average values were higher in the non-diabetic group. HbA 1c and FRAX are inversely correlated with each other: for each incremental percentage point of HbA 1c growth, the FRAX major osteoporotic fracture probability is reduced by 0.915 points and the FRAX hip osteoporotic fracture probability by 1.438 points. The introduction of a correction factor derived from HbA 1c , resulted in mean FRAX values of diabetic patients equivalent to those of non-diabetic subjects., Conclusions: We propose a correction factor derived from HbA 1c that could enhance the predictive ability of fracture risk estimated by the FRAX algorithm in subjects with T2DM.

Objective: The purpose of this study was to investigate the effect of simvastatin on periprosthetic bone mineral density (BMD) in hypercholesterolaemic patients after total hip arthroplasty., Methods: From January 2012 to December 2015, a total of 42 consecutive hypercholesterolaemic patients with total hip arthroplasty were recruited for this study. The simvastatin group was 21 patients (15 males, 6 females) with average age of 69.4 ± 6.6 years treated with simvastatin for one year post-operatively, and the control group was the other 21 patients (12 males, 9 females) who did not take simvastatin. These parameters of the periprosthetic bone mineral density after total hip arthroplasty were collected by dual energy X-ray absorptiometry(DEXA) one week and three, six, 12 months post-operatively., Results: In the control group patients showed significant loss of periprosthetic BMD in ROIs 1, 2, 6, and 7 throughout the study period. The loss of BMD in ROIs 3 and 5 was only significantly observed at three months follow-up and recovered thereafter. There were no significant detected changes of BMD in ROI 4. In the Simvastatin group, the percentage of BMD loss was significantly less (P < 0.05) in ROI 1, 2, 6 and 7 throughout the study period than the control group. The percentage of BMD loss were significant observed in ROI 3 and 5 at three months follow-up, which were also significantly less (P < 0.05) than in the control group. A slight gain of BMD was measured in ROI 4 at 12 months follow-up (1.419%, P < 0.05)., Conclusion: Simvastatin administered for one year post-operatively can effectively prevent periprosthetic bone loss after total hip arthroplasty.

Purpose: As an antioxidant molecule, hydrogen has been received much more attention and reported to be used as the treatment strategy for various diseases. In this study, we hypothesize that systemic delivery of hydrogen saline water may improve the reservation of bone tissue in the tibias and femurs of osteoporotic rats caused by diabetes mellitus (DM), which is characterized by increased levels of oxidative stress and overproducing reactive oxygen species (ROS)., Methods: The animals were divided into three groups of 12 animals and lavaged with normal saline (normal control and DM), or hydrogen saline water (DM + HRS). General status, blood glucose level, tibial and femoral mechanical strength, and micro-CT scans of the proximal tibia were recorded and analyzed., Results: After 12 weeks, the glucose level was significantly decreased in the DM + HRS group compared with that of the DM group. Micro-CT scans showed that bone volume/total volume, connectivity density, trabecular thickness, and trabecular number were significantly increased compared with the DM group. Mechanical results of energy, stiffness and elastic modulus in the DM + HRS group were significantly higher than in the other groups for the tibia and femur., Conclusions: The results indicate that the systemic delivery of hydrogen saline water, which is safe and well tolerated, preserves bone volume and decreases fracture risks in streptozotocin-induced diabetic status rats, whose bone structure or inherent material properties of bone tissues are changed.

To clarify osteoporotic effects of ketogenic diet (KD) on cancellous and cortical bone compared with ovariectomy (OVX) in mice. Forty female C57BL/6J 8-week-old mice were randomly divided into SD+Sham, SD+OVX, KD+Sham, and KD+OVX groups, and fed for 12 weeks. The distal femur of trabecular bone and the middle femur of cortical bone were evaluated with Micro-CT scanning. The maximum bending force and stiffness of the tibia were calculated using a three-point bending test. Osteoblast and osteoclast expression of femur were identified using tartrate-resistant acid phosphatase (TRAP), collagen type I (CoLI), and osteocalcin (OCN) staining. A 2-factor analysis of variance was used to evaluate effects of KD and OVX on radiological, biomechanical, and histological parameters. KD resulted in not only remarkable cancellous bone decline comparable to OVX, but also unique cortical bone reduction. The maximum bending force and stiffness decreased in the KD+Sham and KD+OVX groups but did not change in the SD+OVX group. The KD+OVX led to significantly higher expression in TRAP and noticeably lower expression in CoLI when compared with other groups. Both KD+Sham and SD+OVX prominently increased expression in TRAP, but decreased expression in CoLI. There was no significant difference in OCN among the four groups. The present results suggest that KD compromises both the cancellous and cortical bone architecture of long bones while OVX only in cancellous bone architecture. A combination of KD and OVX may lead to more bone loss.

Bone loss in rheumatoid arthritis (RA) is a key feature both local and systemic. Anti-citrullinated protein antibodies (ACPA) have recently been found to directly induce differentiation and activation of osteoclasts and therefore contribute to periarticular bone loss. The aim of this study was to analyze the effect of ACPA on systemic bone mineral density (BMD) in patients with established RA. This is a cross-sectional study with a single-center RA population. BMD was measured with Dual X-ray absorptiometry at lumbar and femoral sites. ACPA were measured by EIA. Multivariate analysis was performed adjusting for the main confounding variables. One hundred twenty-seven RA patients were enrolled. In univariate analysis, ACPA-positive patients showed lower BMD Z-score (SD below the age- and gender-matched mean reference value) at femoral sites (p < 0.01). A negative correlation between ACPA titer and BMD Z-score at all sites was observed (p < 0.01). The multivariate analysis adjusted for the main confounding variables confirmed the negative effect of ACPA at femoral sites (p < 0.05), but not at lumbar spine BMD. No significant effect of rheumatoid factor has been observed. ACPA have a negative titer-dependent effect on BMD at femoral sites, mainly constituted by cortical bone. ACPA-positive patients, especially if at high titer, should undergo bone investigations and be treated with bone protecting agents. Disease-modifying anti-rheumatic drugs lowering ACPA titer might have positive effects on systemic bone mass.

In an increasingly obese and ageing population, type 2 diabetes (T2DM) and osteoporotic fracture are major public health concerns. Understanding how obesity and type 2 diabetes modulate fracture risk is important to identify and treat people at risk of fracture. Additionally, the study of the mechanisms of action of obesity and T2DM on bone has already offered insights that may be applicable to osteoporosis in the general population. Most available evidence indicates lower risk of proximal femur and vertebral fracture in obese adults. However the risk of some fractures (proximal humerus, femur and ankle) is higher, and a significant number fractures occur in obese people. BMI is positively associated with BMD and the mechanisms of this association in vivo may include increased loading, adipokines such as leptin, and higher aromatase activity. However, some fat depots could have negative effects on bone; cytokines from visceral fat are pro-resorptive and high intramuscular fat content is associated with poorer muscle function, attenuating loading effects and increasing falls risk. T2DM is also associated with higher bone mineral density (BMD), but increased overall and hip fracture risk. There are some similarities between bone in obesity and T2DM, but T2DM seems to have additional harmful effects and emerging evidence suggests that glycation of collagen may be an important factor. Higher BMD but higher fracture risk presents challenges in fracture prediction in obesity and T2DM. Dual energy X-ray absorptiometry underestimates risk, standard clinical risk factors may not capture all relevant information, and risk is under-recognised by clinicians. However, the limited available evidence suggests that osteoporosis treatment does reduce fracture risk in obesity and T2DM with generally similar efficacy to other patients.

Osteoporosis is more frequent in inflammatory bowel disease (IBD) patients. A reduction in bone mineral mass in these individuals is caused not only by inflammatory processes in the bowel, because osteoporosis occurs already in very young IBD patients and in newly diagnosed individuals who have not yet undergone any pharmacological treatment. One of individual determinants of the bone turnover parameters is osteoprotegerin (OPG) encoded by the TNFRSF11B gene. The c.-223C > T polymorphism in this gene has been extensively studied in post-menopausal osteoporosis patients. However, no such studies exist for osteoporosis related to IBD. The aim of our study was to determine whether the c.-223C > T (rs2073617) polymorphism in the 5'UTR region of the gene encoding osteoprotegerin is a functional polymorphism which may change the gene expression and resulting OPG levels, and so be associated with osteopenia and osteoporosis, and impaired bone metabolism in Crohn's disease and ulcerative colitis patients. Our study included 198 IBD patients and 41 healthy controls. Lumbar spine and femoral neck bone mineral density, T-score, Z-score as well as OPG, RANKL, vitamin D, calcium and interleukin 4 and 10 concentrations were determined for all study subjects. Genotyping of the TNFRSF11B polymorphic site was performed by restriction fragment length polymorphism technique. Statistical analyses were conducted using Statistica software. Odds ratios, 95 % confidence intervals, and P values were calculated using the HWE calculator. Our results did not allow determining an unequivocal association between the polymorphic variants of the TNFRSF11B 5'UTR region and a susceptibility to osteoporosis in IBD patients. We have shown, however, that the c.-223T allele was twice as more frequent in Crohn's disease (CD) patients than among controls (OR = 1.99, P value = 0.009). Interestingly, average osteoprotegerin levels in CD patients did not significantly differ from those in controls, whereas in ulcerative colitis patients, OPG levels were significantly lower. We have concluded that low OPG levels may be associated with osteoporosis in ulcerative colitis, but it is not correlated with the c.-223C > T polymorphism in the TNFRSF11B gene. In CD patients, in turn, we observed increased RANKL levels. Our observations confirm different pathogeneses of Crohn's disease and ulcerative colitis as well as different molecular backgrounds of osteoporosis associated with these two diseases., Competing Interests: Iwona Krela-Kaźmierczak, Marta Kaczmarek-Ryś, Aleksandra Szymczak, Michał Michalak, Marzena Skrzypczak-Zielińska, Natalia Drwęska-Matelska, Michalina Marcinkowska, Piotr Eder, Lilianna Łykowska-Szuber, Ewa Wysocka, Krzysztof Linke and Ryszard Słomski have declare that they have no conflict of interest. Ethical Approval The study was approved by the Bioethical Committee of the University of Medical Sciences in Poznań, Poland, under Resolution No. 92/09. Informed consent was obtained from every participant. Human and Animal Rights and Informed Consent All followed procedures were in accordance with the ethical standards of the responsible committee on human experimentation (Bioethical Committee of the University of Medical Sciences in Poznań, Poland, Resolution No. 92/09). Informed consent was obtained from all individual participants included in the study.

A disequilibrium of tumor necrosis superfamily (TNF) members, including the serum osteoprotegerin, soluble receptor activator of nuclear factor-κB ligand, soluble TNF-related apoptosis-inducing ligand and TNF-α, was associated with the occurrence of a reduced skeletal mass and osteoporosis in male patients with end-stage chronic obstructive pulmonary disease (COPD). The purpose of this study was to explore the associations between serum biomarkers of tumor necrosis factor (TNF) superfamily and body and bone compositions in end-stage COPD males. Pulmonary function, T-score at the lumbar spine and femoral neck, lean mass, serum osteoprotegerin (OPG), soluble receptor activator of nuclear factor-κB ligand (sRANKL), TNF-α and its receptors (sTNFR-I, sTNFR-II) and soluble TNF-related apoptosis-inducing ligand (sTRAIL) levels were evaluated in 48 male patients with end-stage COPD and 36 healthy male volunteers. OPG was lower in male COPD patients than in control subjects, whereas sRANKL, TNF-α and its receptors were higher. The serum sTRAIL level showed a tendency to increase compared with that of healthy subjects (P = 0.062). Serum OPG showed a positive correlation with bone density. In contrast, serum TNF-α, sRANKL and sTRAIL were inversely associated with pretransplant bone density. We have noted the appearance of statistically significant inverse relationships between lean mass values and TNF-α, sTNFR-I and II and sRANKL levels in male COPD patients. Moreover, there was a negative correlation between sTRAIL levels with airway obstruction (P = 0.005) and hypercapnia (P = 0.042) in advanced COPD patients. Through a multiple linear regression analysis, our study revealed that a disequilibrium of TNF family members was strongly associated with the occurrence of a reduced skeletal mass and osteoporosis. These results provide further evidence that abnormal levels of TNF superfamily molecules may cause not only a decrease in BMD, but also lower muscle mass in end-stage COPD.

The aim of this study was to evaluate in a large size cohort of SSc patients bone mineral density (BMD) and to analyze its possible determinants. 106 consecutive outpatients affected by SSc were enrolled and completely evaluated for bone metabolism and SSc characteristics. For the statistical analysis, we preferred Z score to BMD or T score since the population was composed of patients of different ages and of both sexes. Mean neck Z score was significantly lower than 0. No significant differences were found for other sites. Female patients were shown to have a total femur and neck Z score significantly lower than 0 (p = 0.028 and p < 0.001, respectively). 13 % of patients had at least one morphometric non-clinical vertebral fracture. In univariate analysis, total femur Z score was lower in female (p = 0.050) and positively correlates with BMI (p = 0.001), neck Z score positively correlates with age (p = 0.016), and whole body Z score positively correlates with BMI (p < 0.001). No correlations were found for lumbar Z score. The multivariate analysis confirmed the positive correlation between BMI and total femur and whole body Z score and between age and neck femur Z score (p = 0.005, p < 0.001 and p = 0.040, respectively). Lung involvement was shown to correlate with a lower whole body Z score in multivariate analysis (p = 0.037). We found a modest risk of low BMD in patients with SSc and the important protective role of BMI. Patients with lung involvement showed lower whole body Z score.

In this study, we compared the long-term effects of different iron chelation regimens (deferoxamine, deferiprone, deferoxamine + deferiprone, and deferasirox) in preventing or reversing endocrinopathy (diabetes mellitus, hypothyroidism, or hypogonadism) and bone disease (measured through DEXA) in 165 adults with β-thalassemia major (TM) (mean age 39.9 ± 8.3 years, 43 % males). After five consecutive years of therapy, patients on deferasirox had the highest decrease in the prevalence of any endocrinopathy compared to other chelators which either had no change (deferiprone and deferoxamine) or had an increase (deferoxamine + deferiprone), p = 0.015. This was attributed to a lower proportion of patients on deferasirox developing new-onset endocrinopathy and higher proportion showing reversal of disease, compared to other chelators. A serum ferritin level of >1300 ng/mL predicted the development of new endocrinopathy (p = 0.025) while a level of <200 ng/mL predicted reversal of existing endocrinopathy (p = 0.147). A significant increase in mean BMD T-score (p < 0.001) and a considerable decrease in osteoporosis prevalence were observed in patients receiving deferasirox but not other chelators. Iron chelation therapy with deferasirox has a role in the prevention of endocrinopathy and reversal of existing disease.

Diffuse idiopathic skeletal hyperostosis (DISH) is a common skeletal disorder in the elderly, which can develop into periosteal hyperostosis and paradoxically into immobilization-associated trabecular osteoporosis. The bone anabolic agent, teriparatide (TPD), seems to be a rational treatment for the immobilization-associated osteoporosis. However, it can lead to development of hyperostosis lesions in DISH patients. Here, we demonstrate TPD effectively treats trabecular osteoporosis while simultaneously promoting ankylosis of the spine in DISH model tiptoe-walking Yoshimura (twy) mice, compared with the ICR mice. Eighteen male twy mice were divided into three groups, and ICR mice were used as a normal control. Subcutaneous injections of TPD or phosphate-buffered saline (PBS) were performed according to three dosing regimens; 40 µg/kg once daily (TPD × 1 group), 40 µg/kg three times daily (TPD × 3 group), and PBS (control; Ctl group). Treatment was commenced at the age of 7 weeks and continued for 5 weeks. Micro-computed tomography (µCT) and histological analysis were performed. Longitudinal µCT study revealed that trabecular bone volume in both the vertebral body and distal femur decreased with time in the Ctl group, but increased dramatically in the TPD × 3 group. The twy mice developed ankylosis of the spine, the progression of which was accelerated with TPD therapy. We also confirmed that TPD therapy promoted ossification of spinal ligaments. Histomorphometrical study revealed that TPD treatment increased bone formation at the vertebrae enthesis region and in the trabecular bone. TPD therapy effectively treats trabecular osteoporosis, but potentially promotes ankylosis of the spine in patients with DISH.

Dairy products provide a package of essential nutrients that is difficult to obtain in low-dairy or dairy-free diets, and for many people it is not possible to achieve recommended daily calcium intakes with a dairy-free diet. Despite the established benefits for bone health, some people avoid dairy in their diet due to beliefs that dairy may be detrimental to health, especially in those with weight management issues, lactose intolerance, osteoarthritis, rheumatoid arthritis, or trying to avoid cardiovascular disease. This review provides information for health professionals to enable them to help their patients make informed decisions about consuming dairy products as part of a balanced diet. There may be a weak association between dairy consumption and a possible small weight reduction, with decreases in fat mass and waist circumference and increases in lean body mass. Lactose intolerant individuals may not need to completely eliminate dairy products from their diet, as both yogurt and hard cheese are well tolerated. Among people with arthritis, there is no evidence for a benefit to avoid dairy consumption. Dairy products do not increase the risk of cardiovascular disease, particularly if low fat. Intake of up to three servings of dairy products per day appears to be safe and may confer a favourable benefit with regard to bone health.

This study aimed to examine the relationship between metabolic syndrome (MetS) and osteoporosis according to muscle mass levels and the joint relationship of MetS and muscle mass with osteoporosis in a representative population-based sample from the Korea National Health and Nutrition Examination Survey in 2010-2011. In 1654 men and 1979 women aged 50-93 years, body composition and bone mineral density at the femur and lumbar spine were measured using dual-energy X-ray absorptiometry. Low- and high-muscle mass groups were identified using the mean sex-specific muscle mass of appendicular muscle mass/height(2). The covariates were age, health behaviors, serum 25-OH vitamin D and parathyroid hormone, calcium intake, and hormone replacement therapy for women. Men and women with MetS (defined by the Adult Treatment Panel III) had 43 and 31% lower odds for osteoporosis, respectively, compared with their MetS-free counterparts after adjusting for muscle mass and covariates. When stratified by muscle mass, MetS was not associated with osteoporosis in men, while associated in women with higher muscle mass (OR 0.65, 95% CI 0.46-0.91). Compared with MetS-free men and women with lower muscle mass, the odds for osteoporosis were 45% and 23, 52 and 15%, and 72 and 46% lower among those with low muscle mass and MetS, high muscle mass without MetS, and high muscle mass and MetS, respectively (P for trend <0.001). Combination of high muscle mass and MetS was associated with lower prevalence of osteoporosis in Korean men and women.

Through a more consistent diagnostics and treatment of osteoporosis, subsequent fractures and associated complications could be reduced in aged patients. Whereas anticoagulants are now standard in the treatment of fractures of the lower extremities to prevent thromboembolic complications in orthopedic surgery and an omission of anticoagulation can be regarded as medical malpractice, the management of osteoporosis following such fractures is very frequently disregarded. Although guidelines for osteoporosis, such as those from the governing body on osteology (Dachverband Osteologie, DVO) from 2014 are not legally binding as such, the breach of this standard of care can constitute a breach of medical obligation by the physician. The omission of osteoporosis diagnostics and initiation of treatment despite appropriate findings after fractures in aged patients, could represent a diagnostic assessment error and severe malpractice in the legal sense. In this case, evidence of a serious malpractice could be associated with civil, criminal and professional claims which could be linked with relevant legal consequences. Regardless of the legal consequences for omission of osteoporosis management following multiple fractures in aged patients, the management of osteoporosis should be an integral component in the treatment of these patients in the future.

Pregnancy and lactation-associated osteoporosis (PAO) is a rare condition with little known pathophysiology. Most cases are diagnosed in the third trimester of pregnancy or in the first weeks postpartum, particularly in first pregnancies. Vertebral fractures are most commonly observed and characterised by prolonged severe pain, functional limitations and a loss of height. Measurements of bone mineral density and biochemical markers of bone remodelling are the clinical methods most commonly used for the management of these patients. However, a bone biopsy with histomorphometric analysis has been considered to be the gold-standard. Few studies have evaluated the histomorphometry in patients with this clinical condition and none of them performed the procedure at the beginning of the clinical assessment. In this study, we report a case of PAO in a 31-year-old postpartum patient who had undergone a twin pregnancy. We describe the clinical, laboratory tests and imaging features. Bone histomorphometry showed a high resorption rate and excellent evolution after 1 year of treatment with intravenous zoledronic acid. Our data suggest that osteoclastogenesis plays a central role in the pathophysiological processes of this disease.

Multiple factors contribute to bone loss in inflammatory diseases such as rheumatoid arthritis (RA), but circulating inflammatory factors and immobilization play a crucial role. Mechanical loading prevents bone loss in the general population, but the effects of mechanical loading in patients with RA are less clear. Therefore, we aimed to investigate whether mechanical stimuli reverse the stimulatory effect of RA serum on osteocyte-to-osteoclast communication. Human primary osteocytes were pretreated with 10 % RA serum or healthy control serum for 7 days, followed by 1 h ± mechanical loading by pulsating fluid flow (PFF). Nitric oxide (NO) and prostaglandin E2 were measured in the medium. Receptor activator of nuclear factor-kappaB ligand (RANKL), osteoprotegerin (OPG), interleukin-6 (IL-6), cyclooxygenase-2 (COX2), matrix-extracellular phosphoglycoprotein (MEPE), cysteine-rich protein 61 (CYR61), and SOST gene expression was quantified by qPCR. Osteoclast precursors were cultured with PFF-conditioned medium (PFF-CM) or static-conditioned medium (stat-CM), and osteoclast formation was assessed. RA serum alone did not affect IL-6, CYR61, COX2, MEPE, or SOST gene expression in osteocytes. However, RA serum enhanced the RANKL/OPG expression ratio by 3.4-fold, while PFF nullified this effect. PFF enhanced NO production to the same extent in control serum (2.6-3.5-fold) and RA serum-pretreated (2.7-3.6-fold) osteocytes. Stat-CM from RA serum-pretreated osteocytes enhanced osteoclastogenesis compared with stat-CM from control serum-pretreated osteocytes, while PFF nullified this effect. In conclusion, RA serum, containing inflammatory factors, did not alter the intrinsic capacity of osteocytes to sense mechanical stimuli, but upregulated osteocyte-to-osteoclast communication. Mechanical loading nullified this upregulation, suggesting that mechanical stimuli could contribute to the prevention of osteoporosis in inflammatory disease.

Patients with systemic lupus erythematosus (SLE) have an increased risk of fracture. We used high resolution peripheral quantitative computed tomography (HR-pQCT) to measure bone geometry, volumetric bone mineral density (vBMD), cortical and trabecular microarchitecture and estimated bone strength by finite element analysis (FEA) at the distal radius and tibia to assess bone characteristics beyond BMD that may contribute to the increased risk of fracture. Thirty-three Caucasian women with SLE (median age 48, range 21-64 years) and 99 controls (median age 45, range 21-64 years) were studied. Groups were comparable in radius regarding geometry and vBMD, but SLE patients had lower trabecular number (-7%, p < 0.05), higher trabecular separation (13%, p < 0.05) and lower FEA-estimated failure load compared to controls (-10%, p < 0.05). In tibia, SLE patients had lower total vBMD (-11%, p < 0.01), cortical area (-14%, p < 0.001) and cortical thickness (-16%, p < 0.001) and higher trabecular area (8%, p < 0.05). In subgroup analyses of the premenopausal participants (SLE n = 21, controls n = 63), SLE patients had significantly lower trabecular bone volume fraction [(BV/TV); -17%, p < 0.01], trabecular number (-9%, p < 0.01), trabecular thickness (-9%, p < 0.05) and higher trabecular separation (13%, p < 0.01) and trabecular network inhomogeneity (14%, p < 0.05) in radius along with lower BV/TV (-15%, p < 0.01) and higher trabecular separation (11%, p < 0.05) in tibia. FEA-estimated bone strength was lower in both radius (-11%, p < 0.01) and tibia (-10%, p < 0.05). In conclusion, Caucasian women with SLE compared to controls had fewer and more widely separated trabeculae and lower estimated bone strength in radius and lower total vBMD, cortical area and thickness in tibia.

Due to the increasing survival of thalassemic patients, osteopathy is a mounting clinical problem. Low bone mass alone cannot account for the high fracture risk described; impaired bone quality has been speculated but so far it cannot be demonstrated noninvasively. We studied bone quality in thalassemia major using trabecular bone score (TBS), a novel texture measurement extracted from spine dual-energy X-ray absorptiometry (DXA), proposed in postmenopausal and secondary osteoporosis as an indirect index of microarchitecture. TBS was evaluated in 124 adult thalassemics (age range 19-56 years), followed-up with optimal transfusional and therapeutical regimens, and in 65 non-thalassemic patients (22-52 years) undergoing DXA for different bone diseases. TBS was lower in thalassemic patients (1.04 ± 0.12 [range 0.80-1.30]) versus controls (1.34 ± 0.11 [1.06-1.52]) (p < 0.001), and correlated with BMD. TBS and BMD values correlated with age, indicating that thalassemia negatively affects both bone quality and quantity, especially as the patient gets older. TBS was 1.02 ± 0.11 [0.80-1.28] in the osteoporotic thalassemic patients, 1.08 ± 0.12 [0.82-1.30] in the osteopenic ones and 1.15 ± 0.10 [0.96-1.26] in those with normal BMD. No gender differences were found (males: 1.02 ± 0.13 [0.80-1.30], females 1.05 ± 0.11 [0.80-1.30]), nor between patients with and without endocrine-metabolic disorders affecting bone metabolism. Our findings from a large population with thalassemia major show that TBS is a valuable tool to assess noninvasively bone quality, and it may be related to fragility fracture risk in thalassemic osteopathy.

This is the first prospective follow-up study to describe the effects of oral alendronate medication on neurofibromatosis 1 (NF1)-related osteoporosis. NF1 is a neurocutaneous skeletal syndrome associated with increased fracture risk and high frequency of osteopenia and osteoporosis. Alendronate is a bisphosphonate drug which inhibits the function of bone-resorbing osteoclasts, ultimately leading to an increase in bone mineral density (BMD) and reduction in fracture risk. However, in vitro studies have shown that NF1 osteoclasts display insensitivity to apoptotic signals caused by bisphosphonates. Our aim was to monitor the effects of alendronate medication in patients with NF1. Five men and one woman, aged 28-76 years, with NF1-related osteoporosis were enrolled to the study. Study participants did not have other conditions and were not taking any medication known to affect bone. The medication included a weekly dose of 70 mg alendronate and a daily 20 μg vitamin D supplementation. After 23 months of follow-up, BMD was increased in five out of six patients, but the increase was not statistically significant. Serum levels of the bone turnover markers CTX and PINP were reduced, suggesting slower bone remodeling, as expected. An unexpected result was that serum levels of the osteoclast activity marker TRAP5b did not change during the follow-up. One new stress fracture of the tibia was documented during the alendronate therapy. Even though the study group was small, the findings of the current study (one new fracture and one patient with decreased BMD) call for a larger study to assess the efficacy of bisphosphonates in NF1-related osteoporosis.

In human immunodeficiency virus (HIV)-infected patients, tenofovir disoproxil fumarate (TDF) may cause hypophosphatemia leading to osteomalacia due to renal phosphate wasting. Fibroblast growth factor 23 (FGF23) may play a role in this setting. We present an HIV-infected patient with TDF-induced profound hypophosphatemia, Fanconi syndrome, osteomalacia, and bilateral hip fracture. Routine serum biochemistry was assessed by standard methods. The plasma FGF23 concentration was measured at Mayo Laboratories (Scottsdale, AZ, USA). Bone mineral density (BMD) was measured using a Hologic Discovery densitometer. At presentation, the patient's plasma C-terminal FGF23 was 2,760 reference units (RU)/mL (15 times upper limit of normal; reference interval [RI] ≤ 180 RU/mL), serum phosphate was 0.58 (RI 0.8-1.6 mmol/L), and TmPO4/GFR was 95%. DXA at the lumbar spine showed a Z score of -4.0. Vitamin D3 and oral phosphate were administered, and TDF was discontinued. After 4 months off TDF, lumbar spine BMD significantly increased by 12% (Z score -3.5); by 6 months the plasma C-terminal FGF23 declined to 1.8 times the upper limit of normal, and both urine and serum phosphate levels normalized. By its marked elevation and subsequent near normalization, FGF23 may be responsible for a component of the phosphate wasting syndrome in these patients. The time course of resolution was 6 months. As expected, with calcium, vitamin D, and phosphate management, BMD significantly improved with resolution of osteomalacia. Clinicians should be aware of this side effect of TDF and the time course of its resolution.

The aim of this study was to examine the relationship between aortic calcification (AC) and the risk of osteoporosis for a community of residents in China. We conducted a 5-year prospective study on 1,729 Chinese elderly subjects. An AC scale (ACS) was determined semiquantitatively from baseline lateral radiographs of the lumbar spine. Dual-energy X-ray absorptiometry was used to determine bone mineral density (BMD). Only subjects who completed the study were included in the final analysis; 432 subjects (25.0 %) developed osteoporosis. The BMD of vertebrae, femoral neck, and the total hip in the Q4 quartile of the ACS (ACS > 6) was lower when compared with the Q1 quartile (ACS = 0, p < 0.05). Cox proportional hazards model analysis showed that ACS (Q4), BMD, CTX, current smoking, and daily drinking were associated with increased risk of osteoporosis. A higher ACS was associated with an increased risk of osteoporosis in both women and men. The present study found that AC carried a higher risk of osteoporosis.

Recent studies have highlighted a significant association between the severity of atherosclerosis and bone mineral density (BMD) among healthy subjects, although its connection to angiographically determined peripheral artery disease (PAD) has never been investigated. We evaluated the connection between the angiographic severity and site specificity of peripheral atherosclerosis and osteoporosis among patients with chronic lower limb ischemia. In our cross-sectional study we investigated 172 patients with PAD. The anatomic sites of the lesions were analyzed. The severity of atherosclerosis was diagnosed using the Bollinger angiographic score (BS). BMD was measured at the lumbar spine (l-BMD) and at femoral (f-BMD) and radial (r-BMD) sites by dual-energy X-ray absorptiometry. Dyslipidemia, the level of vitamin D(3), and different bone turnover markers were also noted. Among PAD patients, regardless of the lesion site, we did not find any association between BMD and BS. Among patients with iliac disease, BS was associated with l-BMD (p = 0.038, r = -0.467) and with f-BMD (p = 0.002, r = -0.642). The level of r-BMD among patients with iliac disease was not associated with BS (p = 0.233, r = -0.306). We did not find any difference between the group of patients with and that without dyslipidemia and low or normal levels of vitamin D(3). Our results show a connection between the severity of atherosclerosis and osteoporosis among patients with PAD, specific to the site of the lesion. The findings regarding dyslipidemia, bone markers, and site specificity support the hypothesis that reduced blood flow is the key factor responsible for the inverse association of BMD with atherosclerosis.

Cerebrotendinous xanthomatosis (CTX) is known to be associated with osteoporosis and a higher incidence of bone fractures. However, the underlying pathogenesis is still unknown, and the effects of long-term replacement therapy with chenodeoxycholic acid (CDCA) on bone mineral density (BMD) have not been fully investigated. We studied 11 CTX patients aged 13-43 years. We performed dual-energy X-ray absorptiometry and assessed serum cholestanol and 25-hydroxyvitamin D (25-OHD) concentrations both at the time of diagnosis and after long-term treatment with CDCA. At baseline, we found low BMD in nine patients, cholestanol elevation in all subjects, and 25-OHD decrease in nine. After a mean follow-up time of 30 months (range 24-36), no substantial clinical changes including bone fractures occurred; and we detected a significant increase of both planar and volumetric BMD as well as normalization of plasma cholestanol levels and increase of serum 25-OHD. Densitometric improvement following CDCA introduction was not correlated to changes of biochemical parameters. Our study confirms the presence of low bone mass in CTX and demonstrates that long-term CDCA treatment increases bone mineral content. In this respect, improvement of vitamin D intestinal absorption secondary to bile acid restoration could play an important role. Moreover, our data strongly suggest the utility of periodic bone density evaluation in CTX patients.

Aim: Reasonable application of laboratory parameters in prevention, diagnosis, treatment and therapy monitoring of osteoporosis., Target Groups: Physicians from different specialist disciplines (general medicine, geriatrics, gynaecology, urology, internal medicine-especially endocrinology and metabolism, nephrology, laboratory medicine, rheumatology, nuclear medicine, orthopaedics, paediatrics, rehabilitation and physical medicine, radiology, social medicine, transplantation medicine, accident surgery), moreover social insurances, hospitals and self-help groups., Background: Evaluation of aetiology of bone disorders, widening of the therapeutic spectrum for diseases of bone and knowledge on biochemical markers of bone turnover. Improvements in judging the success of therapy and in monitoring the compliance of patients. Research perspectives., Bases: Scientific literature and guidelines, consensus meetings. RÉSUMÉ: Basic and specialized laboratory investigations are important in differentiation between primary and secondary osteoporosis for an adequate therapy. Biochemical markers of bone turnover are an additional aid in evaluation of individual fracture risk. These markers identify responders to bone therapy faster than surveillance of bone mineral density, which helps to improve patient's compliance too. Characteristics, preanalytic precautions and applications are presented for selected markers of bone resorption and formation and for parameters regulating bone metabolism.

Persons with inflammatory bowel disease (IBD) are reported to have a high prevalence of osteoporosis and reduced bone mineral density (BMD) and to be at higher risk of fracture. The course of BMD loss over time is poorly characterized in persons with IBD. Eighty-six persons, stratified by age, were enrolled from a population-based longitudinal IBD cohort study to undergo BMD testing at baseline, with final BMD testing a mean of 4.3 years later. The proportion of subjects with significant change in BMD at the lumbar spine, total hip, and femoral neck was assessed, as were clinical, biochemical, and anthropomorphic changes. Vertebral radiographs were also obtained at baseline and at the end of follow-up in those aged 50 years and above to detect vertebral fractures. The change in BMD seen in this cohort of IBD patients was similar to the expected rate of BMD loss in the general population. Age >50 years, decreasing body mass index (BMI), and corticosteroid use were most notably correlated with BMD loss. Subjects aged <50 years did not have statistically significant declines in BMD. IBD symptom activity scores correlated poorly with BMD loss. Vertebral fractures were uncommon, with only two subjects out of 41 >50 years old developing a definite radiographic fracture over the course of follow-up. No major nonvertebral fractures were observed. Patients with IBD do not appear to have significantly accelerated BMD loss. Older age, decreasing BMI, and corticosteroid use may identify IBD patients at greater risk for BMD loss.

Background: There are conflicting opinions in the literature about whether pregnancy influences maternal bone density or osteoporosis development. The study aim was to investigate whether there is a significant alteration in maternal bone density during normal pregnancy., Methods: Bone mass of 200 pregnant women aged 22-42 years was measured twice with quantitative ultrasonometry (QUS) of the heel (Os calcaneum). The first measurement was performed between the 10th and 22nd week of pregnancy, follow-up of 149 women took place 0-9 days postpartum. A questionnaire focusing on data affecting bone metabolism and bone turnover was handed out at the first visit., Results: Median reduction in speed of sound (SOS) was 11 m/s at follow-up indicating a decline of the stiffness during pregnancy. No significant correlation was found between lactation period and the obtained values for stiffness, SOS, T score and Z score. For broadband ultrasonographic attenuation, there was a statistically significant difference (p < 0.05) between women who had and had not breastfed. Parameters from patients with a family history of osteoporosis (n = 30) compared to patients without did not reveal statistical significance during pregnancy. Glucocorticoid therapy, nicotine consumption, physical exercise and nutrition was not statistically significant (p > 0.05). SOS value of women with a twin pregnancy was different over the study period (p < 0.05)., Conclusion: A reduction in bone mass is possible during pregnancy. Routine evaluation of the bone density in all pregnant women does not seem to be justified; however, it is reasonable in women who present with risk factors. These women could be screened with QUS.

Intramuscular injection with botulinum toxin A (BTX) leads to a transient paralysis of the muscles, resulting in a rapid loss of muscle mass and function as well as rapid bone loss (disuse osteoporosis). The purpose of this study was to investigate the temporal development and the site specificity of BTX-induced immobilization on bone strength at five skeletal sites. Three-month-old rats (n = 108) were randomized into nine groups: one served as baseline, while four were injected with BTX and four with saline in the right hind-limb musculature. Animals were killed after 1, 2, 3, or 4 weeks. BTX-induced a significant loss of rectus femoris muscle mass (-61%) and muscle cell cross-sectional area (-59%) as well as bone strength at the femoral neck (-31%), femoral diaphysis (-6%), distal femoral metaphysis (-17%), proximal tibial metaphysis (-31%), and tibial diaphysis (-13%) after 4 weeks. Muscle atrophy occurred in parallel with the bone loss at the femoral neck and proximal tibia, whereas it occurred earlier than the bone loss at the other skeletal sites. At the proximal tibial metaphysis BTX significantly decreased BV/TV (-10%), trabecular thickness (-13%), and bone formation (MS/BS -25%, BFR/BS -50%) and increased osteoclast covered surfaces (+97%) after 4 weeks. In conclusion, BTX-induced a time-dependent loss of bone strength. Moreover, the loss of bone strength differed significantly at the five tested skeletal sites.

Skeletal metastases affect a large percentage of the cancer population and contribute to a marked decrease in their quality of life and survival, in particular in elderly population. A future end-point of bone-protecting therapy is the demonstration of its ability to prevent or improve results in the treatment of metastatic disease, enlarging their clinical indications in metastatic and osteoporotic setting with different schedules. In this chapter we will discuss on pharmacokinetic and pharmacodynamic interactions of bisphosphonates in elderly, and the preclinical and clinical evidences of anticancer activity of bone-targeted therapies will be critically described. The clinical results of new targeted therapies (such as rank/rankl/OPG inhibition) will be reported both in bone metastatic and in adjuvant settings. Finally, the prevention of cancer treatment-induced bone loss (CTIBL) represents both in young and more in old patients an emerging issue in the bone health care. For this reason, this chapter will discuss the results of current therapies in this clinical setting.

Disorders of bone and mineral metabolism are common complications in chronic kidney disease (CKD) patients and lead to significantly increased fracture risk, morbidity, and mortality of cardiovascular disease due to ectopic calcifications, contributing to a worsening prognosis. Bone strength is determined by not only bone mineral density but also bone quality, which is dependent on bone collagen cross-links. Collagen cross-links are classified into enzymatic immature and mature types and nonenzymatic advanced glycation end products (AGEs). Pentosidine is well established as one of the AGEs that accumulates markedly in CKD patients. The chemistry, function, and clinical relevance of cross-links have been revealed, whereas bone quality and the relationship with bone mineralization in CKD patients are not clear. We performed transiliac bone biopsies on 22 dialysis patients (mean age 56 ± 9 years) with severe secondary hyperparathyroidism and measured cross-links by evaluating bone histomorphometry. Cross-links data were compared with age-matched non-CKD subjects (mean age 58 ± 8 years, n = 17). Enzymatic collagen cross-links were formed to a similar extent compared with non-CKD subjects and showed a positive correlation with plasma intact parathyroid hormone. Pentosidine was remarkably increased in dialysis patients and inversely correlated with bone-formation rate/bone volume and mineral apposition rate. This study suggests that AGE collagen cross-links strongly associate with disorders of bone metabolism in dialysis patients.

Objective: To demonstrate MR imaging findings in the cortical and trabecular bone as well as marrow changes in patients with disuse osteoporosis (DO)., Materials and Methods: Sixteen patients (14 men, 2 women, aged 27-86 years) with clinical and radiographic evidence of DO of a lower limb joint (10 knees, 6 ankles) with MR examination of the same joint performed within a 1-month period were selected, as well as 16 healthy volunteers (7 men, 9 women, aged 25-75 years, 10 knees and 6 ankles). MR imaging findings of the bone marrow were analyzed by 2 musculoskeletal radiologists in consensus regarding: diffuse or focal signal alteration, reinforcement of vertical or longitudinal trabecular lines, and presence of abnormal vascularization., Results: All patients (100%,16/16) with DO presented MR imaging abnormalities of the bone marrow, such as: accentuation of vertical trabecular lines (50%, 8/16), presence of subchondral lobules of fat (37.5%, 6/16), presence of horizontal trabecular lines (31%, 5/16), prominence of bone vessels (25%, 4/16), and presence of dotted areas of high signal intensity on T2-weighted fat-suppressed sequences (12.5%, 2/16). Such MR findings did not appear in the control individuals., Conclusion: There are several MR imaging findings in bones with DO that range from accentuation of vertical and horizontal marrow lines, presence of subchondral lobules of fat, prominent bone vascularization and the presence of dotted foci of high signal intensity on T2-weighted fat-suppressed sequences. Recognition of these signs may prove helpful in the identification of DO as well as distinguishing these findings from other entities.