Measured Bone Turnover Markers Research Articles

Osteoporosis and low bone mass among schizophrenia and bipolar disorder: A cross-sectional study with newly diagnosed, drug-naïve subjects

BackgroundA growing body of data shows that schizophrenia (SCZ) and bipolar disorder (BD) have substantial metabolic risks; however, few studies have focused on bone metabolism. This study aimed to assess the prevalence and associated influencing factors of low bone mass and osteoporosis in SCZ and BD before pharmacological effects occur. Methods108 healthy controls (HCs) and drug-naïve individuals with SCZ (n = 56) and BD (n = 130) had their lumbar spine (L1–L4) and left femur (Neck/Trochanter/Ward's triangle) bone mineral density (BMD) determined using dual-energy X-ray absorptiometry. Besides, we measured bone turnover markers (BTMs) levels, including procollagen I N-terminal propeptide, osteocalcin, and C-terminal cross-linking telopeptide of type I collagen in different groups. ResultsIndividuals with SCZ and BD had significantly lower BMD and significantly higher prevalence of low bone mass and osteoporosis compared with HCs. In the main observation regions of the total lumbar (F = 18.368, p < 0.001) and left femur (F = 14.790, p < 0.001), BMD was lower in individuals with SCZ and BD than HCs, with SCZ showing lower BMD than BD. The osteocalcin (H = 11.421, p = 0.003) levels were significantly higher in SCZ and BD than HCs.Binary regression analysis showed that SCZ or BD was an independent risk factor for low bone mass and osteoporosis. In addition, sex, age, and BTMs also influenced the occurrence of low bone mass and osteoporosis. LimitationsCross-sectional study. ConclusionThe results findings of the study might contribute to our understanding of the increased risk of bone metabolism in SCZ and BD. Clinical trial registrationwww.chictr.org.cn, identifier ChiCTR1900021379.

Biochemical Markers of Calcium and Bone Metabolism during and after Lactation in Ugandan Women with HIV on Universal Maternal Antiretroviral Therapy.

We reported accentuated lactational decreases in areal bone mineral density and only partial skeletal recovery after lactation in Ugandan women with HIV (WWH) initiated on tenofovir disoproxil fumarate-based antiretroviral therapy (TDF-based ART) during pregnancy compared to women without HIV (REF). WWH also had higher breast milk calcium in the first months of lactation. To investigate the mechanisms, we measured bone turnover markers (bone resorption: C-terminal telopeptide [CTX]; bone formation: procollagen type 1 N-terminal propeptide [P1NP], bone-specific and total alkaline phosphatase [BALP, TALP]), hormones (parathyroid hormone [PTH], intact fibroblast growth factor 23 [FGF23], 1,25-dihydroxyvitamin D [1,25(OH)2 D]), vitamin D status (25-hydroxyvitamin D [25OHD]), and indices of mineral metabolism and renal function. Blood and urine samples collected at 36 weeks of gestation, 14 and 26 weeks of lactation, and 3-6 months after lactation were analyzed. Mean 25OHD was >50 nmol/L throughout. Both groups experienced similar biochemical changes during pregnancy and lactation to women in other settings, but within these patterns, the two groups differed significantly. Notably, WWH had higher PTH (+31%) and lower 1,25(OH)2 D (-9%) and TmP/GFR (-9%) throughout, lower P1NP (-27%) and plasma phosphate (-10%) in pregnancy, higher CTX (+15%) and BALP (+19%), and lower eGFR (-4%) during and after lactation. P1NP/CTX ratio was lower in WWH than REF in pregnancy (-21%), less so in lactation (-15%), and similar after lactation. Additionally, WWH had lower plasma calcium (-5%), lower FGF23 (-16%) and fasting urinary calcium (-34%) at one or both lactation timepoints, and higher fasting urinary phosphate (+22%) at 26 weeks of lactation and after lactation. These differences resemble reported TDF effects, especially raised PTH, increased bone resorption, decreased bone formation, and decreased renal function, and may explain the observed differences in bone mineral density and breast milk calcium. Further studies are needed to determine whether HIV and TDF-based ART have long-term consequences for maternal bone health and offspring growth. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

The Relationship Between Stress Fractures and Bone Turnover Markers Is Unclear in Athletic and Military Populations: A Critically Appraised Topic

Clinical Scenario: Having an indication of how bone is remodeling in response to training load could help identify athletes and military personnel at increased stress fracture (SFx) risk. Direct assessment of bone remodeling is impractical. Biochemical markers of bone turnover are used as an indirect measure of bone remodeling and have potential to inform prevention and treatment efforts. To date, the relationship between bone turnover markers and SFxs in athletes or military personnel remains unclear. Clinical Question: Are SFxs related to bone turnover markers in athletes and military personnel? Summary of Key Findings: Seven met eligibility criteria. In five studies, an association between SFxs and bone turnover markers existed. Clinical Bottom Line: The evidence supporting a relationship between SFxs and bone turnover markers in athletes and military personnel is mixed. While five of the seven studies reported some type of relationship, no studies prospectively measured bone turnover markers in a group of athletes or military personnel without an SFx or without SFx history and followed them over time to reassess bone turnover markers upon SFx occurrence. Strength of Clinical Recommendation: In accordance with the Strength of Recommendation Taxonomy, Grade C is the most appropriate strength of recommendation rating.

Research on biochemical indexes of bone metabolism in bipolar disorder: A cross-sectional study with newly diagnosed, drug-naïve patients

BackgroundIn recent years, the metabolic abnormalities associated with bipolar disorder (BD) have attracted people's attention. However, clinical studies on bone metabolism in individuals with BD are unavailable. This study was designed to assess biochemical indexes of bone metabolism and related influencing factors. MethodsWe measured bone turnover markers (BTMs), including procollagen Ⅰ N-terminal propeptide (PⅠNP), osteocalcin (OC) and C-terminal cross-linking telopeptide of type I collagen (CTX-I), and index of calcium and phosphorus metabolism in 100 drug-naïve individuals with BD (DSM-5) and 91 healthy volunteers. Besides, sociodemographic and clinical assessment were collected. Between-group comparisons and within subgroup analysis were performed. ResultsThe PⅠNP (t = 3.715, p < 0.001), OC (t = 2.117, p = 0.036), parathyroid hormone (PTH, t = 3.877, p < 0.001), vitamin D (t = 2.065, p = 0.041), insulin (t = 4.208, p < 0.001) and insulin resistance (t = 2.888, p = 0.004) levels in the drug-naive BD group was significantly higher than those in the healthy control (HC) group. The level of calcium (t = −2.124, p = 0.035) in the drug-naive BD group was significantly lower than that of the HC group. But OC and vitamin D loses statistical significance after Bonferroni correction. However, there was no significant difference in the CTX-I level between the two groups. There are gender differences in the level of BMTs in individuals with BD, but this phenomenon was not found in the HC subgroup. It is shown that diagnosed BD, gender, age and BMI may affect the PINP levels through multiple linear regression analysis. ConclusionThe biochemical indexes of bone metabolism in drug-naive individuals with BD were more active than that of the healthy controls in a sample from the Chinese Han nationality. The finding provides new evidence for our understanding of bone metabolism in individuals with BD.

Bone Metabolism, Bone Mineral Content, and Density in Elite Late Teen Female Sprinters.

With intensive training, bone injuries are a major concern for athletes. To assess bone condition, we often measure bone turnover markers, bone mineral content and density; however, in junior athletes, it is not easy to distinguish changes caused by bone injuries from those caused by growth, because the metabolism is increased in both cases. Moreover, although some studies have examined female endurance athletes, knowledge regarding changes in static and dynamic bone conditions in late teen athletes is limited. In this study, we measured the bone mineral content and density, as well as bone turnover markers, in 40 elite female sprinters in their late teens. Whole body mode dual-energy X-ray absorptiometry was performed to measure bone mineral content and density. Blood samples were collected to determine bone resorption and formation markers at the end of track season in 2016 and during the same period of the following year. Body weight and bone mineral content significantly increased, and tartrate-resistant acid phosphatase type 5b, bone-type alkaline phosphatase, and osteocalcin significantly decreased after a year. Furthermore, the rate of change in bone mineral content was higher in younger athletes, indicating that bone growth approaches completion in the late teen years and that bone metabolism accordingly decreases.

Time-Restricted Eating for 12 Weeks Does Not Adversely Alter Bone Turnover in Overweight Adults.

Weight loss is a major focus of research and public health efforts. Time-restricted eating (TRE) is shown to be effective for weight loss, but the impact on bone is unclear. Short-term TRE studies show no effect on bone mineral density (BMD), but no study has measured bone turnover markers. This secondary analysis examined the effect of 12 weeks of TRE vs. unrestricted eating on bone turnover and BMD. Overweight and obese adults aged 18–65 y (n = 20) were randomized to TRE (ad libitum 8-h eating window) or non-TRE. Serum N-terminal propeptide of type I collagen (P1NP), cross-linked N-telopeptide of type I collagen (NTX), and parathyroid hormone (PTH) levels were measured and dual-energy X-ray absorptiometry (DXA) scans were taken pre- and post-intervention. In both groups, P1NP decreased significantly (p = 0.04) but trended to a greater decrease in the non-TRE group (p = 0.07). The treatment time interaction for bone mineral content (BMC) was significant (p = 0.02), such that BMC increased in the TRE group and decreased in the non-TRE group. Change in P1NP was inversely correlated with change in weight (p = 0.04) overall, but not within each group. These findings suggest that TRE does not adversely affect bone over a moderate timeframe. Further research should examine the long-term effects of TRE on bone.

Gender-Affirming Hormone Therapy and Bone Health: Do Different Regimens Influence Outcomes in Transgender Adults? A Narrative Review and Call for Future Studies.

Gender-affirming hormone therapy (GAHT) influences bone health in transgender individuals. Several hormone preparations and administration routes are available for GAHT, but no studies have compared clinical and laboratory bone health measures across different GAHT regimens. We searched PubMed (MEDLINE), Embase, and Google Scholar for studies measuring bone turnover markers and bone mineral density before and during GAHT in transgender adults. We summarized bone health data by hormone type and administration route (estrogen or testosterone; oral, transdermal/percutaneous, intramuscular). Among trans women, we also examined outcomes among regimens containing different adjunctive agents (antiandrogens or gonadotropin-releasing hormone analogs). Most hormone preparations maintained or increased areal bone mineral density among trans adults taking GAHT for at least 12 months from baseline. Different bone turnover markers were measured across studies, and we were unable to compare or comment on the direct influence of selected hormone preparations on these clinical laboratory measures. Larger and uniformed studies are needed to measure volumetric bone mineral density and biomarkers of bone metabolism in trans adults taking standardized GAHT regimens.

THE IMPACT OF REGULAR FOOTBALL TRAINING ON BONE TURNOVER MARKERS

Introduction The condition of the skeleton is important not only in the perspective of osteoporosis prevention, but also as a factor affecting the frequency of injuries excluding physical activity. Monitoring the impact of specific sports on osteoclasts and osteoblasts acitivity allows optimization of programming of physical activity limiting the risk of bone mineralization disorders. The review analyzes available papers on the impact of regular football training on skeletal physiology changes analyzed by measuring bone turnover markers in the body. Aim Determining the impact of regular football training on bone mass regulation by analyzing bone turnover markers. Material and methods PubMed and SPORTDiscus with Full Text databases were searched using the keyword combination “the name of team sport” + bone turnover. There is no clinical trials about bone turnover markers among handball, hockey, basketball and volleyball players in the available literature that meet the inclusion criteria, so the topic of the review was narrowed down to football (soccer). After applying the exclusion criteria, five studies were qualified. Results In the analyzed papers, the concentration of osteocalcin, N-terminal procollagen type I extension propeptide and C-terminal telopeptide of type I collagen in blood increased as a result of regular football training. In 3 papers statistically significant (p &lt; 0.05) increases were noted. Conclusions Football training can stimulate bone metabolism, being an effective and attractive form of bone fracture prevention, regardless of your level of sport. Due to the limited availability of studies, there is a high need for further studies describing the impact of physical activity on bone metabolism.

The effect of vitamin MK-7 on bone mineral density and microarchitecture in postmenopausal women with osteopenia, a 3-year randomized, placebo-controlled clinical trial.

Vitamin K is a cofactor in the carboxylation of osteocalcin (OC) and carboxylated OC promotes mineralization of bone. Clinical studies suggest that vitamin K2 prevents bone loss. The aim of the study was to investigate the effect of vitamin K2 as an add-on to calcium and vitamin D supplementation on osteocalcin, bone mass, and microarchitecture in postmenopausal women. We conducted a randomized placebo-controlled double-blinded clinical trial, including 142 postmenopausal women with osteopenia who received vitamin K2 (375μg MK-7) or placebo daily for 3years. Both groups received vitamin D3 (38μg/day) and calcium (800mg/day). We measured bone turnover markers in serum and bone mineral density and microarchitecture by DXA and HRpQCT. Undercarboxylated osteocalcin decreased in the MK-7-group (- 65.2 ± 23.5%) (mean ± SD) compared with the placebo group (- 0.03 ± 38.5%), p < 0.01 after 1year. After 3years, aBMD decreased at all sites without differences between the MK-7 and placebo-treated women (p > 0.09). aBMD decreased at the total hip by 1.5 ± 2.5% and 2.4 ± 2.7% in the MK-7 and the placebo groups, respectively, at the femoral neck by 1.5 ± 3.5% and 1.0 ± 5.0% in the MK-7 and the placebo groups, respectively, and at the lumbar spine by 1.8 ± 3.9% and 1.1 ± 3.1% in the MK-7 and the placebo groups, respectively. Changes in bone turnover markers were also similar between the two groups.We have previously reported improved microarchitecture with MK-7 after 1year. However, changes in microstructure over 3years were similar between the two groups, as assessed by both HRpQCT and DXA trabecular bone score. Treatment with MK-7375μg daily as an add-on to calcium and vitamin D increased carboxylation of osteocalcin. However, treatment of postmenopausal women with osteopenia for 3years did not affect biochemical markers of bone turnover, bone mineral density, or bone microarchitecture. The study was registered at Clinicaltrial.gov : NCT01922804 .

Erişkin hastalarda genel ve rejyonel anestezinin kemik belirteçleri ve kırık iyileşmesi üzerine uzun dönem etkileri

Purpose: Bone metabolism can be monitored quantitatively by measuring bone turnover markers in serum and/or urine. We aimed to investigate long-term effect of the type of the anesthesia on bone turnover markers and fracture healingMaterials and Methods:Thirty patients with American Society of Anesthesiologist physical status I-II whom were aged 40-70 years, scheduled for hip fracture were recruited. Patients were divided into the two groups as general anesthesia and regional anesthesia. Only morphine and tramadol were used for postoperative analgesia till the 12th weeks. Serum bone-specific alkaline phosphatase, osteocalcine, β-C terminal telopeptide and urine β-C terminal telopeptide levels were measured at preoperative, 4.th week and 12.th week of fracture. Results:A total of 25 patients were eligible for the study. There were no statistically significant between groups for values of bone turnover markers at the time point of preoperative, 4.th and 12.th weeks. With using linear regression analysis, serum β-CTX levels at 12.th week can be predict by 4.th weeks β-CTX levels (R2: 0.944) and urine β-CTX levels at 12.th week can be predicted by first week level.Conclusion: This pilot study showed that both general and regional anesthesia has similar effect on bone turnover markers and fracture healing.

Excessive Vitamin E Intake Does Not Cause Bone Loss in Male or Ovariectomized Female Mice Fed Normal or High-Fat Diets

Background: Animal studies on the effects of vitamin E on bone health have yielded conflicting and inconclusive results, and to our knowledge, no studies have addressed the effect of vitamin E on bone in animals consuming a high-fat diet (HFD).Objective: This study aimed to evaluate the effect of excessive vitamin E on bone metabolism in normal male mice and ovariectomized female mice fed a normal diet (ND) or HFD.Methods: In the first 2 experiments, 7-wk-old male mice were fed an ND (16% energy from fat) containing 75 (control), 0 (vitamin E-free), or 1000 (high vitamin E) mg vitamin E/kg (experiment 1) or an HFD (46% energy from fat) containing 0, 200, 500, or 1000 mg vitamin E/kg (experiment 2) for 18 wk. In the third experiment, 7-wk-old sham-operated or ovariectomized female mice were fed the ND (75 mg vitamin E/kg) or HFD containing 0 or 1000 mg vitamin E/kg for 8 wk. At the end of the feeding period, blood and femurs were collected to measure bone turnover markers and analyze histology and microcomputed tomography.Results: In experiments 1 and 2, vitamin E intake had no effect on plasma alkaline phosphatase (ALP), tartrate-resistant acid phosphatase (TRAP) activity, or bone formation, resorption, or volume in femurs in mice fed the ND or HFDs. In experiment 3, bone volume was significantly reduced (85%) in ovariectomized mice compared with that in sham-operated mice (P < 0.05), but it did not differ among mice fed the 3 diets. Plasma ALP and TRAP activities and bone formation and resorption in femur were similar among ovariectomized mice fed the HFD containing 0 or 1000 mg vitamin E/kg.Conclusions: The results suggest that excess vitamin E intake does not cause bone loss in normal male mice or in ovariectomized or sham-operated female mice, regardless of dietary fat content.

Thyrotropin serum levels are differentially associated with biochemical markers of bone turnover and stiffness in women and men: results from the SHIP cohorts.

In two large German population-based cohorts, we showed positive associations between serum thyrotropin (TSH) concentrations and the Fracture Risk Assessment score (FRAX) in men and positive associations between TSH concentrations and bone turnover markers in women. The role of thyroid hormones on bone stiffness and turnover is poorly defined. Existing studies are confounded by differences in design and small sample size. We assessed the association between TSH serum concentrations and bone stiffness and turnover in the SHIP cohorts, which are two population-based cohorts from a region in Northern Germany comprising 2654 men and women and 3261 men and women, respectively. We calculated the bone stiffness index using quantitative ultrasound (QUS) at the calcaneus, employed FRAX score for assessment of major osteoporotic fractures, and measured bone turnover markers, N-terminal propeptide of type I procollagen (P1NP), bone-specific alkaline phosphatase (BAP), osteocalcin, and type I collagen cross-linked C-telopeptide (CTX) in all subjects and sclerostin in a representative subgroup. There was no association between TSH concentrations and the stiffness index in both genders. In men, TSH correlated positively with the FRAX score both over the whole TSH range (p < 0.01) and within the reference TSH range (p < 0.01). There were positive associations between TSH concentrations and P1NP, BAP, osteocalcin, and CTX (p < 0.01) in women but not in men. There was no significant association between TSH and sclerostin levels. TSH serum concentrations are associated with gender-specific changes in bone turnover and stiffness.

P236 Relationship Between Bone Mineral Density And Bone Turnover Markers In Severe Asthma Patients On Systemic Corticosteroids

Objectives Measure bone turnover markers (BTM) CTx, P1NP and bone-specific alkaline phosphatase (BsALP) in a severe asthma population using systemic corticosteroids (SCS). Assess bone mineral density (BMD) change in regional severe asthma clinics. Background Severe asthma often requires regular SCS use. SCS cause several adverse effects including reduced bone metabolism; resorption is increased and formation is decreased resulting in osteoporosis. DXA scans monitor BMD in the hip and spine every 3–5 years. BMD decrease is treated with bone sparing medication (BSM), but treatment is retrospective and response takes years to assess. BTM represent markers of systemic bone metabolism and may offer a more efficient alternative. CTx is a resorption marker, P1NP and BsALP are formation markers. Method Patients attending Manchester or Belfast severe asthma clinic with two or more DXA scans were identified from case files. We measured BTM in Manchester severe asthma patients and a control group of Manchester severe asthma patients requiring less than 3 courses of steroids per year. Using case files we collected data including DXA scan results, SCS use and osteoporosis risk factors. Results BMD change and BTM did not correlate overall (patients n = 78, controls n = 18) but correlated negatively in patients where the most recent DXA was Conclusion This study has confirmed that BTM may be potentially used as a surrogate for BMD measurement; however a more a prospective study where BTM are measured at the time of two DXA scans which are years apart is required.

The association between critical illness and changes in bone turnover in adults: a systematic review.

Critical illness may lead to altered bone turnover and associated adverse health outcomes. This systematic review found moderate evidence for a positive association between critical illness and increased bone turnover. Prospective cohort studies that identify the extent and risk factors for critical illness related bone loss are required. Intensive care patients face health issues that extend beyond their critical illness and result in significant morbidity and mortality. Critical illness may result in altered bone turnover due to associated immobilisation, inflammation, exposure to medications that effect bone and calcium metabolism, and endocrine dysfunction. The aim of this study was to synthesise the existing evidence for altered bone turnover in adults admitted to intensive care. A literature search using MEDLINE and EMBASE was performed from 1965 to March 2013. Reviewed studies investigated the relationship between critical illness and evidence of altered bone turnover (bone turnover markers, bone mineral density, or fracture). Studies were rated upon their methodological quality, and a best-evidence synthesis was used to summarise the results. Four cohort and seven case-control studies were identified for inclusion, of which five studies were rated as being of higher methodological quality. Ten of the studies measured bone turnover markers, and one study fracture rate. Findings were consistent across studies, and best-evidence analysis resulted in a conclusion that moderate evidence exists for an association between critical illness requiring admission to intensive care and altered bone turnover. A positive association between critical illness requiring intensive care admission and bone turnover exists, although data are limited, and the risk factors and the nature of the relationship are not yet understood. Prospective cohort studies that identify risk factors and extent of critical illness related bone turnover changes are required.

Decreased Bone Turnover Markers in Children on Long‐Term Parenteral Nutrition (PN) for Intestinal Failure (IF)

Metabolic bone disease (MBD) is a well-recognized but poorly understood complication of long-term parenteral nutrition (PN). Bone histomorphometry in adults has provided useful information but does not provide quantitative measures of bone resorption and is to invasive for children. Measurement of bone turnover markers provides an alternative less invasive approach. We therefore aimed to measure bone turnover markers in children on long-term PN for intestinal failure (IF), and to compare them to age- and gender-matched controls. Serum concentrations of osteocalcin (OC), bone-specific alkaline phosphatase (BSAP), and c-telopeptide (CTx) were measured in IF patients treated at a multidisciplinary intestinal rehabilitation and home PN program at the Hospital for Sick Children, Toronto, Canada. Age- and gender-matched control participants were recruited for comparison. A total of 13 IF patients and 20 control participants were recruited. IF patients had lower serum OC and CTx concentrations when compared with controls: 42.43 ± 11.54 vs 68.39 ± 20.95 µg/L (P < .01) and 7.454 ± 2.17 vs 9.246 ± 1.92 (P < .05; mean ± SD) µg/L for OC and CTx, respectively. In a subgroup of 9 IF patients for whom BMD was available, OC and CTx concentration were negatively correlated to BMD (g/cm(2)) and BMD z score. Bone turnover markers may be useful indicators for identifying children on long-term PN at risk of MBD. Further studies are needed to validate the current results and determine the factors that influence the occurrence and evolution of MBD in children on PN.

Measurement of Urinary N-Telopeptides and Serum C-Telopeptides from Type I Collagen Using a Lateral Flow-Based Immunoassay

Measuring bone turnover markers could detect early stages of osteoporosis and early responses to anti-osteoporotic treatments. Currently, commonly used bone turnover markers, N-telopeptides (NTx) and C-telopeptides (CTx), are measured using ELISA tests, which demands time and increases cost. Bone turnover markers need to be measured more easily for general use. Lateral flow-based immunoassay would be an appropriate method for this context. This study was performed to investigate the precision of a newly developed lateral flow-based immunoassay for measuring the urinary NTx and serum CTx, and their correlations with ELISA measurements. Urine NTx and serum CTx concentrations were determined by photoscan of newly developed strips, using a lateral flow-based immunoassay for 36 subjects (mean age 66.2 years, SD 7.5 years; four males and 32 females). Repeated measurement of urinary NTx and serum CTx were performed three times, using this technology for a precision test. The correlation of the lateral flow-based immunoassay with the ELISA measurements was analyzed. Precision of the newly developed lateral flow based immunoassay was 0.974 (ICC, 95% confidence interval, 0.955 to 0.986) and 0.995 (ICC, 95% confidence interval, 0.991 to 0.997) for urinary NTx and serum CTx, respectively. The correlation of lateral flow based immunoassay with ELISA was 0.913 for urinary NTx and 0.872 for serum CTx. These results suggest that measuring the urinary NTx and serum CTx, using a lateral flow-based immunoassay, is a relevant method for point-of-care testing and screening of bone resorption markers.

Low Bone Turnover and Low BMD in Down Syndrome: Effect of Intermittent PTH Treatment

Trisomy 21 affects virtually every organ system and results in the complex clinical presentation of Down syndrome (DS). Patterns of differences are now being recognized as patients’ age and these patterns bring about new opportunities for disease prevention and treatment. Low bone mineral density (BMD) has been reported in many studies of males and females with DS yet the specific effects of trisomy 21 on the skeleton remain poorly defined. Therefore we determined the bone phenotype and measured bone turnover markers in the murine DS model Ts65Dn. Male Ts65Dn DS mice are infertile and display a profound low bone mass phenotype that deteriorates with age. The low bone mass was correlated with significantly decreased osteoblast and osteoclast development, decreased bone biochemical markers, a diminished bone formation rate and reduced mechanical strength. The low bone mass observed in 3 month old Ts65Dn mice was significantly increased after 4 weeks of intermittent PTH treatment. These studies provide novel insight into the cause of the profound bone fragility in DS and identify PTH as a potential anabolic agent in the adult low bone mass DS population.

Cortical Consolidation of the Radius and Tibia in Young Men and Women

Bone size, geometry, density, and microarchitecture are important determinants of bone strength. By understanding how these properties change during skeletal development, we can better understand bone fragility. The aim of the study was to compare the geometry, microarchitecture, and strength of the radius and tibia in men and women at the end of adolescence and in young adulthood and to relate these properties to biochemical bone turnover markers and bone regulatory hormones. We conducted a cross-sectional study of 116 healthy men and women ages 16-18 (n = 56) and 30-32 (n = 60) yr. We used high-resolution peripheral quantitative computed tomography to measure bone size, geometry, and microarchitecture at the distal radius and tibia and micro-finite element modeling to estimate bone strength. We measured bone turnover markers (β C-terminal telopeptide of type I collagen and amino-terminal propeptide of type I procollagen) and hormones known to affect bone metabolism (estradiol, testosterone, IGF-I, and PTH). Bone strength was greater in men than in women, and at the radius it was greater in men ages 30-32 yr than ages 16-18 yr. The gender difference was due to greater cortical perimeter, trabecular area, and trabecular density in men. The age difference was due to greater cortical thickness and cortical tissue mineral density and lower cortical porosity. IGF-I was related to two of these five key properties at the radius (cortical perimeter and cortical thickness). None of the hormones were predictors of density or structure at the tibia. Cortical modeling of long bones continues beyond the end of adolescence. IGF-I may be a determinant of this process at the radius.

Reduction of volumetric bone mineral density in postmenopausal women with hepatitis C virus-correlated chronic liver disease: A peripheral quantitative computed tomography (pQCT) study

BackgroundThe prevalence of osteoporosis in chronic liver disease (CLD) varies considerably among the studies, depending on patient selection and diagnostic criteria. We aimed to measure bone turnover markers and volumetric bone mineral density (BMD) in a group of postmenopausal women with CLD using both dual energy X-ray absorptiometry (DXA) and peripheral quantitative computed tomography (pQCT), in comparison with age-matched healthy subjects. MethodsThirty-five postmenopausal patients with HCV-correlated CLD and 35 healthy postmenopausal women, as controls, underwent a DXA scan at lumbar and femoral level and a pQCT measurement of the nondominant forearm. Serum concentrations of biochemical markers relevant to bone turnover were also measured. ResultsPatients showed no differences in DXA values either at lumbar or femoral level compared to controls. On the contrary, pQCT geometrical (cortical cross-sectional area) and volumetric (total and trabecular volumetric BMD) parameters were significantly reduced in the CLD women. Also the Strength–Strain Index (SSI), an estimate of diaphyseal bone resistance to bending and torsion, was significantly lower in patients than in controls. Patients with CLD presented an unbalanced bone turnover, with increased bone resorption markers. ConclusionsThe bone geometrical and volumetric parameters measured in our CLD postmenopausal women, by pQCT, show a reduced bone mineral quality and stiffness. Conversely, DXA-measurements seem unable to appreciate the bone alterations in these patients. This would encourage further studies to validate pQCT analysis as a diagnostic tool for a correct estimate of bone involvement in CLD.

Characteristics of bone metabolism markers during the healing of osteoporotic versus nonosteoporotic metaphyseal long bone fractures: a matched pair analysis.

The activity and metabolism of fracture healing can be monitored quantitatively by measuring bone turnover markers (BTMs) in serum or urine. However, in osteoporotic bone, the exact metabolism processes during the healing of metaphyseal fractures remain unknown. There is no diagnostic approach which currently allows dynamic insight into the fracture healing processes in order to monitor the progression of healing and to assist in therapeutic decision making. Between March 2007 and February 2009, 30 patients over 50years of age who suffered a metaphyseal fracture were included in our study. The levels of the osteoanabolic marker BAP (bone-specific alkaline phosphatase) and osteocatabolic marker β-CTX [crosslinked C-(CTX)-telopeptide-of-type-I-collagen] were monitored during the fracture healing of osteoporotic and nonosteoporotic fractures for a duration of 8weeks. After an initial decrease of BAP in the first week, the BAP level steadily increased through the fourth week in both groups. The levels of BAP in the osteoporotic group surpassed the healthy group. β-CTX steadily increased in healthy bone up to the fourth week; in osteoporotic bone, β-CTX first increased and, thereafter, decreased from the first week onwards. In this work, the first molecular biological aspects of osteoporotic fracture healing have been uncovered, helping to explain the mechanisms of delayed fracture healing in osteoporotic bone. The early decrease of reduced β-CTX as well as elevated BAP during the healing process may be the first aspects within the delayed healing of osteoporotic bone. Further studies are necessary in order to achieve more detailed insight to fracture healing and to ascertain the progression of fracture healing as being essential (criteria) for therapeutic decision making.