Bone turnover in pregnancy, measured by urinary CTX, is influenced by vitamin D supplementation and is associated with maternal bone health: findings from the Maternal Vitamin D Osteoporosis Study (MAVIDOS) trial.

BACKGROUND: The pattern of change in maternal bone turnover throughout pregnancy is poorly characterized. OBJECTIVES: We investigated changes across pregnancy in a marker of maternal bone resorption, urinary C-terminal telopeptide of type I collagen (CTX), the influence of gestational vitamin D supplementation, and associations between CTX and maternal postnatal bone indices. METHODS: MAVIDOS (the Maternal Vitamin D Osteoporosis Study) is a randomized, double-blind, placebo-controlled trial of 1000 IU cholecalciferol/d compared with placebo from 14 weeks of gestation to birth. Maternal second-void urinary α- and ß-CTX were measured (ELISA) at 14 and 34 weeks of gestation; DXA was performed within 2 wk postpartum. The Mann-Whitney Rank Sum test, Spearman's rank correlation, and linear regression were used to compare median CTX values within and between groups from early to late pregnancy, and associations with maternal bone outcomes. RESULTS: In total, 372 women had CTX and 25-hydroxyvitamin D [25(OH)D] measured in early and late pregnancy. CTX at 14 and 34 weeks of gestation were correlated in both placebo (r = 0.31) and cholecalciferol (r = 0.45) groups (P < 0.0001). Median CTX increased from 14 to 34 weeks of gestation in both groups (n = 372 total) [placebo (n = 188): from 223.6 to 449.7 µg/mmol creatinine; cholecalciferol (n = 184): from 222.3 to 419.3 µg/mmol creatinine; P = 0.03 for placebo compared with cholecalciferol difference in CTX at 34 weeks of gestation]. The conditional mean ± SD increase in CTX [z-score (SD)] from early to late pregnancy was greater in the placebo group (n = 188) than in the cholecalciferol group (n = 184) (placebo: 0.16 ± 0.92; cholecalciferol: -0.16 ± 1.06; P-difference < 0.01). Higher CTX at 34 weeks of gestation was associated, similarly in both groups, with lower maternal total hip and lumbar spine bone mineral content and bone mineral density (BMD) (e.g., lumbar spine BMD: ß = -0.02 g · cm-2 · SD-1 increase in CTX; 95% CI: -0.027, -0.002 g · cm-2 · SD-1; P = 0.02, n = 283). CONCLUSIONS: Maternal urinary CTX, a bone resorption marker, rises through pregnancy, although to a lesser degree with gestational cholecalciferol supplementation, and is inversely associated with maternal bone mass postpartum.This trial was registered at www.isrctn.com as ISRCTN 82927713 and eudract.ema.europa.eu as EudraCT 2007-001716-23.

Potential of biomarkers during pharmacological therapy setting for postmenopausal osteoporosis: a systematic review.

BACKGROUND: Biochemical markers of bone turnover (BTMs), such as the bone alkaline phosphatase (bALP), procollagen type I N propeptide (PINP), serum cross-linked C-telopeptides of type I collagen (bCTx), and urinary cross-linked N-telopeptides of type I collagen (NTx), are used to manage therapy monitoring in osteoporotic patients. This systematic review analyzed the potential of these BMTs in predicting the clinical outcomes in terms of BMD, t-score, rate of fractures, and adverse events during the therapy setting in postmenopausal osteoporosis. METHODS: All randomized clinical trials (RCTs) reporting data on biomarkers for postmenopausal osteoporosis were accessed. Only articles reporting quantitative data on the level of biomarkers at baseline and on the outcomes of interest at the last follow-up were eligible. RESULTS: A total of 36,706 patients were retrieved. Greater values of bALP were associated with a greater rate of vertebral (P = 0.001) and non-vertebral fractures (P = 0.0001). Greater values of NTx at baseline were associated with a greater rate of adverse events at the last follow-up (P = 0.02). Greater values of CTx at baseline were associated with a greater rate of adverse events leading to discontinuation (P = 0.04), gastrointestinal adverse events (P = 0.0001), musculoskeletal adverse events (P = 0.04), and mortality (P = 0.04). Greater values of PINP at baseline were associated with greater rates of gastrointestinal adverse events (P = 0.02) at the last follow-up. CONCLUSION: The present analysis supports the adoption of BMTs during pharmacological therapy setting of patients suffering from osteoporosis. LEVEL OF EVIDENCE: I, systematic review of RCTs.

Changes in levels of cartilage oligomeric proteinase and urinary C-terminal telopeptide of type II collagen in subjects with knee osteoarthritis after dextrose prolotherapy: A randomized controlled trial.

OBJECTIVE: To assess the effects of dextrose prolotherapy in patients with knee osteoarthritis on the levels of serum cartilage oligomeric proteinase and urinary C-terminal telopeptide of type II collagen, and on the Western Ontario McMaster Universities Index and numerical rating scale score for pain. METHODS: A randomized controlled trial, in which participants were randomly allocated into 2 groups, receiving injections of either hyaluronic acid or dextrose prolotherapy. The hyaluronic acid group received 5 injections, 1 each on weeks 1, 2, 3, 4 and 5, and the dextrose prolotherapy group received 3 injections, 1 each on weeks 1, 5 and 9. Serum cartilage oligomeric proteinase, urinary C-terminal telopeptide of type II collagen, Western Ontario McMaster Universities Index score, and numerical rating scale score for pain were measured at baseline and 3 weeks after the last injection. Comparative analysis was conducted using Wilcoxon test within groups and analysis of covariance (ANCOVA) test between groups. RESULTS: A total of 47 participants (21 allocated to hyaluronic acid, 26 allocated to dextrose prolotherapy) completed the protocol. Both interventions resulted in significant improvements in numerical rating scale scores for pain, total Western Ontario McMaster Universities Index scores, and its subscales score. However, the dextrose prolotherapy outperformed hyaluronic acid in numerical rating scale score for pain and level of urinary C-terminal telopeptide of type II collagen, with score changes differences of 0.93 (p = 0.042) and 0.34 (p = 0.048), respectively. No significant changes in level of serum cartilage oligomeric proteinase were found in either group. CONCLUSION: Dextrose prolotherapy is an alternative injection therapy for knee osteoarthritis, which was found to be associated with a significant reduction in urinary C-terminal telopeptide of type II collagen compared with hyaluronic acid injection. Neither injection method resulted in reduced serum cartilage oligomeric proteinase.

Associations between bone turnover markers and bone mineral density in older adults.

OBJECTIVE: To examine the associations between bone turnover markers (BTMs) and bone mineral density (BMD) in older adults aged 60-85 years. METHODS: A total of 1124 men (mean age, 69.1 years) and 1203 women (mean age, 70.7 years) from the National Health and Nutrition Examination Survey 1999-2002 were included in this cross-sectional analysis. Independent variables were serum bone-specific alkaline phosphatase (sBAP) and urinary N-telopeptide (uNTx), which are biomarkers of bone formation and resorption, respectively. Outcome variable was lumbar BMD. The associations of sBAP and uNTx levels with lumbar BMD was examined using multivariable linear regression models. RESULTS: sBAP was negatively associated with lumbar BMD in each multivariable linear regression model, and this negative association was stable in both men and women men (men: ß = -0.0028, 95% CI: -0.0046 to -0.0010; women: ß = -0.0039, 95% CI: -0.0054 to -0.0023). On the other hand, uNTx was negatively associated with lumbar BMD after adjustment of relevant covariables (ß = -0.0328, 95% CI: -0.0523 to -0.0133). However, in the subgroup analysis stratified by gender, this negative association remained only in older women (ß = -0.0491, 95% CI: -0.0751 to -0.0231). CONCLUSION: Our study suggested that elevated sBAP and uNTX levels correlated with decreased lumbar BMD, especially in older women. This finding indicated that maintaining BTMs at low levels may be beneficial to bone health for older adults.

The relationship between urinary C-Telopeptide fragments of type II collagen, knee joint load, pain, and physical function in individuals with medial knee osteoarthritis.

OBJECTIVE: Considering the osteoarthritis (OA) model that integrates the biological, mechanical, and structural components of the disease, the present study aimed to investigate the association between urinary C-Telopeptide fragments of type II collagen (uCTX-II), knee joint moments, pain, and physical function in individuals with medial knee OA. METHODS: Twenty-five subjects radiographically diagnosed with knee OA were recruited. Participants were evaluated through three-dimensional gait analysis, uCTX-II level, the WOMAC pain and physical function scores, and the 40m walk test. The association between these variables was investigated using Pearson's product-moment correlation, followed by a hierarchical linear regression, controlled by OA severity and body mass index (BMI). RESULTS: No relationship was found between uCTX-II level and knee moments. A significant correlation between uCTX-II level and pain, physical function, and the 40m walk test was found. The hierarchical linear regression controlling for OA severity and BMI showed that uCTX-II level explained 9% of the WOMAC pain score, 27% of the WOMAC physical function score, and 7% of the 40m walk test. CONCLUSION: Greater uCTX-II level is associated with higher pain and reduced physical function and 40m walk test performance in individuals with medial knee OA.

Clinically Relevant Molecular Biomarkers for Use in Human Knee Osteoarthritis: A Systematic Review.

OBJECTIVE: Biomarkers in osteoarthritis (OA) could serve as objective clinical indicators for various disease parameters, and act as surrogate endpoints in clinical trials for disease-modifying drugs. The aim of this systematic review was to produce a comprehensive list of candidate molecular biomarkers for knee OA after the 2013 ESCEO review and discern whether any have been studied in sufficient detail for use in clinical settings. DESIGN: MEDLINE and Embase databases were searched between August 2013 and May 2018 using the keywords "knee osteoarthritis," "osteoarthritis," and "biomarker." Studies were screened by title, abstract, and full text. Human studies on knee OA that were published in the English language were included. Excluded were studies on genetic/imaging/cellular markers, studies on participants with secondary OA, and publications that were review/abstract-only. Study quality and bias were assessed. Statistically significant data regarding the relationship between a biomarker and a disease parameter were extracted. RESULTS: A total of 80 studies were included in the final review and 89 statistically significant individual molecular biomarkers were identified. C-telopeptide of type II collagen (CTXII) was shown to predict progression of knee OA in urine and serum in multiple studies. Synovial fluid vascular endothelial growth factor concentration was reported by 2 studies to be predictive of knee OA progression. CONCLUSION: Despite the clear need for biomarkers of OA, the lack of coordination in current research has led to incompatible results. As such, there is yet to be a suitable biomarker to be used in a clinical setting.

Predicting bone turnover following tobacco exposure using bone alkaline phosphatase and N-telopeptide biomarkers and possible variability and effect modification of these markers by race/ethnicity.

Introduction: This study investigated the systemic response of serum bone alkaline phosphatase (SBAP) and urinary N-telopeptide (UNTX) to tobacco exposure and environmental tobacco smoke (ETS) and the possible effect modification (and variability) of this response by racial/ethnic origin.Methods: Data (n = 5411) were obtained from the National Health and Nutrition Examination Survey, with data analysis done on adults aged ≥ 20 years. Outcome variables were SBAP and UNTX. Independent variable was tobacco exposure measured using serum cotinine levels and adjusted for covariates. Generalized linear models were used to explore associations.Results: A percentage increase in log transformed serum cotinine was associated with a 0.005 percentage increase in log transformed SBAP (CI: 0.002, 0.008) and 0.02 percentage increase in log transformed UNTX (CI: -0.01, 0.04) with interaction between cotinine and race/ethnicity (p = 0.01). Stratifying by race/ethnicity, tobacco exposure was associated with significant decreases in UNTX among non-Hispanic Whites - 0.008(-0.014, -0.002) and Mexican Americans -0.014 (-0.025, -0.002) only. Categories of serum cotinine were associated with a monotonic increase in SBAP (p for trend <0.001) and monotonic non-linear decrease in UNTX (p for trend > 0.05).Conclusions: Tobacco and environmental tobacco exposure are associated with SBAP and increased bone formation. The response of UNTX to these exposures is modified by race/ethnicity with non-Hispanic Whites and Mexican-Americans less sensitive to the resorptive effects of tobacco exposure on bone.

Utility of urinary type I collagen cross-linked N-telopeptide as a prognostic indicator in breast cancer patients with bone metastases.

BACKGROUND: Breast cancer patients with bone metastases are usually managed with bone modifying agents, such as zoledronic acid and denosumab, and some bone turnover markers (BTMs) have been recognized as prognostic indicators in such patients. Although several studies have demonstrated the validity of BTMs as prognostic markers in patients treated with zoledronic acid, few studies have reported the utility of BTMs with denosumab treatment. In this study, we evaluated whether urinary N-telopeptide of type I collagen (u-NTX) can be a prognostic indicator in patients treated with denosumab. METHODS: Thirty-six breast cancer patients newly diagnosed with bone metastases were evaluated retrospectively. Patients were treated with denosumab and anti-cancer drugs. u-NTX levels were measured 1 month before and after administration of denosumab, and the ratio of u-NTX levels before and after denosumab (change ratio) was assessed for its association with prognosis. RESULTS: Levels of u-NTX decreased after denosumab administration in all patients except for one. The median value of the u-NTX change ratio was 0.766. Based on the change ratio, patients were divided into either a "high group" (n = 18) or a "low group" (n = 18). The low group showed significantly shorter overall survival (OS) compared with the high group (low group 15.0 months; high group 54.0 months; P = 0.012). Multivariate analysis indicated that the "low group" was an independent prognostic factor for OS (P = 0.028). CONCLUSION: We demonstrated that the u-NTX change ratio in denosumab-treated breast cancer patients with bone metastases can be a prognostic marker.

The effects of dietary changes on bone markers in postmenopausal vertebral osteopenia.

BACKGROUND & AIMS: Nutrition is one of the most important environmental factors affecting the formation of osteopenia. The purpose of this study was to investigate the effects of dietary changes on bone formation and bone resorption markers of postmenopausal women with vertebral osteopenia. METHODS: In this study, 108 women with postmenopausal vertebral osteopenia were included. Patients were observed for a month to identify their regular nutritional status. Before intervention, blood and urine samples were taken from all patients. Then, 2-day food consumption records were taken and the patients were divided into 4 groups. Different types of diets (opposite of their regular diets) were prepared for these groups (1: control, 2: reduced-carbohydrate, 3: reduced-protein, 4: reduced-sodium) and followed for 3 months. At the end of follow-ups, blood and urine samples were taken again and changes in osteocalcin (OC) and N-terminal telopeptide (NTX) levels were examined. RESULTS: According to biochemical analysis, there was a significant decrease (p < 0,001) in OC levels in reduced protein group and an increase (p > 0,05) in reduced carbohydrate group. When NTX levels were assessed, a significant decrease (p < 0.001) in the reduced carbohydrate group and a significant increase in the reduced protein group (p < 0.05) were found. CONCLUSION: Our findings show that reduced carbohydrate diet protected whereas, reduced protein diet negatively affected bone health. Osteopenic individuals were thought to be able to improve bone health and their quality of life by early dietary intervention.

Elevated levels of circulating fibroblast growth factor 23 with hypercalcemia following discontinuation of denosumab.

We report a case of a 47-year-old woman with hypercalcemia 6 months after discontinuation of denosumab. She underwent right mastectomy for breast cancer and had received aromatase inhibitor and denosumab therapy for 5 years. Thirst, appetite loss, and bilateral ankle pain began few months after cessation of denosumab. She was admitted to the hospital for hypercalcemia and hyperthyroidism 6 months after the last dose of denosumab. Laboratory investigations revealed hypercalcemia, normophosphatemia, normal renal function, and elevated levels of fibroblast growth factor 23 (FGF-23). Serum tartrate-resistant acid phosphatase 5b and urine N-terminal cross-linked telopeptide of type I collagen were both elevated, and bone scintigraphy revealed increase of whole bone uptake. Radiological examinations showed no recurrence of breast cancer or tumors that secrete intact PTH or FGF-23. Hypercalcemia, which lasted for 1 month, was refractory to discontinuation of the aromatase inhibitor, normalization of thyroid hormone levels, saline hydration, and calcitonin administration, but was effectively treated with zoledronic acid. Abnormal uptake on bone scintigraphy and ankle pain both resolved a few months after treatment, and hypercalcemia has not recurred in the ensuing 2 years. In conclusion, we found elevated levels of circulating FGF-23 with hypercalcemia following the discontinuation of denosumab. FGF-23 might be a surrogate marker for massive bone resorption triggered by discontinuation of long-term denosumab treatment.

Urinary cross-linked carboxyterminal telopeptide, a bone resorption marker, decreases after vaso-occlusive crises in adults with sickle cell disease.

People with sickle cell disease often report severe bone pain with repeated bouts of vaso-occlusive crises, but the extent of skeletal injury incurred during these painful episodes remain unclear. We sought to quantify bone degradation by comparing urinary concentrations of carboxyterminal cross-linked telopeptide of type I collagen (CTX-1), a well-described marker of bone resorption, in a prospective cohort of 52 adults with sickle cell disease enrolled in the Sickle Cell Pain Markers Study. We also questioned if changes in urinary CTX-1 concentrations correlated with changes in hemolysis and inflammatory markers measured both during and after resolution of a painful vaso-occlusive episode. Thirty-one of the 52 adults enrolled in the study had paired urine samples for CTX-1 analysis. Urinary CTX-1, corrected for urine creatinine, significantly decreased from a mean of 3.45 µg/mmol during vaso-occlusive crises to 2.62 µg/mmol at recovery (p = 0.01). Thus, increased bone loss appears to correlate with acute vaso-occlusive crises in sickle cell disease. Our finding that urinary CTX-1 can be used to probe bone degradation in sickle cell disease provides an important new tool for diagnosing and monitoring response to therapy for people with sickle cell-related bone loss.

Association between polycyclic aromatic hydrocarbons exposure and bone turnover in adults.

BACKGROUND: Cigarette smoking is a risk factor of osteoporosis and bone fracture. Tobacco smoke contains several polycyclic aromatic hydrocarbons. Thus, we hypothesized that environmental polycyclic aromatic hydrocarbon exposure is associated with bone loss and fracture risk. The present study examined the association between polycyclic aromatic hydrocarbon exposure and bone turnover in the general adult population. METHODS: A total of 1408 eligible participants from the National Health and Nutrition Examination Survey (NHANES 2001-2006) were included in this cross-sectional analysis. The levels of urinary N-telopeptide and serum bone-specific alkaline phosphatase, which are biomarkers of bone resorption and formation, respectively, were assessed. Meanwhile, polycyclic aromatic hydrocarbon exposure was evaluated using the concentrations of urinary polycyclic aromatic hydrocarbon metabolites. The association between polycyclic aromatic hydrocarbon exposures and N-telopeptide, and bone-specific alkaline phosphatase levels was assessed using a multivariate linear regression model. RESULTS: All polycyclic aromatic hydrocarbon metabolites except 3-phenanthrene were significantly associated with increased N-telopeptide levels (P < 0.05) after adjustment of relevant covariables. However, no significant relationship was observed between polycyclic aromatic hydrocarbon metabolites and bone-specific alkaline phosphatase levels. This relationship remained significant after the participants were assessed according to sex (P < 0.05). Additionally, all polycyclic aromatic hydrocarbon metabolites showed a positive association with N-telopeptide levels in participants aged <60 years (P < 0.05). CONCLUSION: Polycyclic aromatic hydrocarbon exposure is associated with increased bone resorption among the general adult population in the United States. Further studies must assess the potential mechanisms associated with the adverse effects of polycyclic aromatic hydrocarbon exposure on bone loss.

Rapid Progression of Knee Pain and Osteoarthritis Biomarkers Greatest for Patients with Combined Obesity and Depression: Data from the Osteoarthritis Initiative.

OBJECTIVE: To compare the progression of biochemical biomarkers of osteoarthritis (OA), knee pain, and function between nonobese patients (NON), obese patients without depression (OBESE), and obese patients with comorbid depression (O + D). DESIGN: Utilizing the FNIH OA Biomarkers Consortium dataset, we categorized knee OA patients into NON, OBESE, and O + D groups based on body mass index and Center for Epidemiological Studies-Depression (CES-D) scores. Subjective symptoms (Knee injury and Osteoarthritis Outcome Score Quality of Life subscale (KOOS QOL), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain and Physical Function scores, and the Short Form-12 (SF-12) Physical Component Score [PCS]) and objective measures of cartilage degradation and bone remodeling (urinary CTXII and CTXIα) were compared among groups at baseline and 2-year follow-up. RESULTS: Of the 600 patients, 282 (47%) were NON, 285 (47.5%) OBESE, and 33 (5.5%) O + D. The O + D group had significantly worse pain and function both at baseline and 2-year follow-up (P < 0.001 for all comparisons) as evidenced by self-reported measures on KOOS QOL, WOMAC Pain, WOMAC Physical Function, and SF-12 PCS. The O + D group also demonstrated significant increases in CTXII (P = 0.01) and CTXIα (P = 0.005), whereas the NON and OBESE groups did not. CONCLUSIONS: The combination of inferior knee pain, physical function, and significantly greater increases in biomarkers of cartilage degradation and bony remodelling suggest a more rapid progression for obese OA patients with comorbid depression. The link between systemic disease, inflammatory burden, and progressive cartilage degradation is in line with increasing concerns about a degenerative synovial environment in early osteoarthritic knees that progress to treatment failure with biologic restoration procedures.

Unexpected rapid increase in bone mineral density by bisphosphonate therapy after multiple spinal fractures: a case report.

BACKGROUND: Osteoporosis is a serious disease that causes bone fragility fractures and increases mortality. Bisphosphonates are the first-line drugs for osteoporosis. However, the gains in bone mineral density by use of bisphosphonates alone are limited. CASE PRESENTATION: We describe the clinical outcome of a Japanese woman with osteoporosis treated with bisphosphonates after multiple spinal fractures. After 3 years of treatment with the bisphosphonate alendronate, her lumbar bone mineral density and bilateral hip bone mineral density markedly increased by 61.9% and 32.5%, respectively. CONCLUSION: We considered that our patient's multiple fractures had caused a decrease in bone mineral density, which naturally improved with fracture healing to enhance the increase in bone mineral density with bisphosphonate treatment.

A bone resorption marker as predictor of rate of change in femoral neck size and strength during the menopause transition.

We assessed whether a bone resorption marker, measured early in the menopause transition (MT), is associated with change in femoral neck size and strength during the MT. Higher levels of bone resorption were associated with slower increases in femoral neck size and faster decreases in femoral neck strength. PURPOSE: Composite indices of the femoral neck's ability to withstand compressive (compression strength index, CSI) and impact (impact strength index, ISI) forces integrate DXA-derived femoral neck width (FNW), bone mineral density (BMD), and body size. During the menopause transition (MT), FNW increases, and CSI and ISI decrease. This proof-of-concept study assessed whether a bone resorption marker, measured early in the MT, is associated with rates of change in FNW, CSI and ISI during the MT. METHODS: We used previously collected bone resorption marker (urine collagen type I N-telopeptide [U-NTX]) and femoral neck strength data from 696 participants from the Study of Women's Health Across the Nation (SWAN), a longitudinal study of the MT in a multi-ethnic cohort of community-dwelling women. RESULTS: Adjusted for MT stage (pre- vs. early perimenopause), age, body mass index (BMI), bone resorption marker collection time, and study site in multivariable linear regression, bone resorption in pre- and early perimenopause was not associated with transmenopausal decline rate in femoral neck BMD. However, each standard deviation (SD) increase in bone resorption level was associated with 0.2% per year slower increase in FNW (p = 0.03), and 0.3% per year faster declines in CSI (p = 0.02) and ISI (p = 0.01). When restricted to women in early perimenopause, the associations of bone resorption with change in FNW, CSI, and ISI were similar to those in the full sample. CONCLUSIONS: Measuring a bone resorption marker in pre- and early perimenopause may identify women who will experience the greatest loss in bone strength during the MT.

Changes in bone metabolic profile associated with pregnancy or lactation.

Calcium and nutrients are transferred from mothers to fetuses or infants during pregnancy or lactation, respectively, promoting metabolic changes in the mother, many uncharacterized. To evaluate these changes, we undertook two parallel studies. In one we analyzed fourteen clinical cases of vertebral fragility fractures, at or before three months after partum, in mothers who breastfed their infants. In the other, we enrolled 79 additional pregnant subjects, some who chose to breastfeed and others who did not, and analyzed changes in bone metabolic status starting between 34 and 36 weeks of gestation and ending one month after partum. In the larger group, bone-resorbing and bone-forming parameters such as serum TRACP5b and osteocalcin, respectively, significantly increased after partum. Among parameters that changed after partum, serum PTH and the bone-resorbing markers serum TRACP5b and urine NTX were significantly higher in mothers who only breastfed infants compared to mothers who fed infants formula or a mix of both. However, bone-forming parameters were comparable between breastfeeding and non-breast-feeding groups after partum, suggesting that elevated bone-resorption occurs only in the breastfeeding group. Radiographic analysis after partum demonstrated that no subject among the 79 analyzed showed vertebral fractures, even those who breastfed exclusively. Among fracture cases analyzed, subjects exhibited significantly lower bone mineral density than did non-fracture cases in breastfeeding-only subjects. We conclude that bone metabolic status significantly changes over the period between pregnancy and post-partum lactation, and that low bone mineral density seen in a small subset of breastfeeding-only cases likely causes post-partum vertebral fragility fractures.

Bone Biomarker Response to Walking under Different Thermal Conditions in Older Adults.

Endurance exercise can cause a decrease in serum ionized calcium (iCa) and increases in parathyroid hormone (PTH) and c-terminal telopeptide of type I collagen (CTX), which may be due to Ca loss in sweat. PURPOSE: This study aimed to determine whether exercise in a warm environment exaggerates the decrease in iCa and increases in PTH and CTX compared with a cool environment in older adults. METHODS: Twelve women and men 61-78 yr old performed two identical 60-min treadmill bouts at ~75% of maximal heart rate under warm and cool conditions. Serum iCa, PTH, and CTX were measured every 15 min starting 15 min before and continuing for 60 min after exercise. Sweat Ca loss was estimated from sweat volume and sweat Ca concentration. RESULTS: Sweat volume was low and variable; there were no differences in sweat volume or Ca concentration between conditions. iCa decreased after 15 min of exercise, and the change was similar in both conditions. Increases in PTH (warm: 16.4, 95% confidence interval [CI] = 6.2, 26.5 pg·mL; cool: 17.3, 95% CI = 8.1, 26.4 pg·mL) and CTX (warm: 0.08, 95% CI = 0.05, 0.11 ng·mL; cool: 0.08, 95% CI = 0.01, 0.16 ng·mL) from before to immediately after exercise were statistically significant and similar between conditions. Adjusting for plasma volume shifts did not change the results. CONCLUSION: The increases in PTH and CTX, despite the low sweat volume, suggest that dermal Ca loss is not a major factor in the decrease in iCa and increases in PTH and CTX observed during exercise in older adults.

Factors Influencing Serum Homocysteine Levels in Postmenopausal Osteoporotic Females - Comparison to Urinary Collagen Crosslinks.

Purpose: The correlation between serum levels of homocysteine and bone mineral density remains controversial. The aim of this study was to identify the potential factors associated with the levels of serum total homocysteine (S-Hcy) and urinary N-terminal telopeptide of type I collagen (U-NTX) in female osteoporotic patients. Materials and Methods: This cross-sectional study included 163 female osteoporotic patients, aged between 48 and 91 years, who had never been treated with anti-osteoporosis therapy. Background data including spine and hip bone mineral density, ongoing therapy for the metabolic disease, aortic calcification score as evaluated by lateral lumbar X-ray film, and recent fragility fracture history were obtained. S-Hcy, U-NTX levels, and creatinine clearance were measured. Results: Multiple linear regression analysis revealed a significant correlation between S-Hcy levels and aortic calcification score (p = 0.022), creatinine clearance (p = 0.004), and recent fracture history (within 1 year after fracture) (p = 0.028); conversely, U-NTX levels correlated significantly with total hip bone mineral density (p < 0.0001) and recent fracture history (p = 0.0007). Conclusions: S-Hcy levels had no correlation with bone mineral density, but were associated with the degree of aortic calcification, renal function, and fracture events. These confounding factors should be taken into consideration when the relationship between S-Hcy and bone mineral density is discussed.

Protein biomarkers in serum and urine for determining presence or absence of hip dysplasia in a canine model.

This study compares serum and urine concentrations of relevant protein biomarkers among adult dogs with or without radiographic canine hip dysplasia (CHD). Adult (≥2 years of age), client-owned dogs (n = 74) radiographically categorized as having at least "good" hips (n = 49) or having "mild," "moderate," or "severe" hip dysplasia (n = 25) by the Orthopedic Foundation for Animals (OFA). Urine and serum samples were obtained from each dog at a single time-point and processed and analyzed for relevant protein biomarkers. Urinary concentrations of CTX-II (p < 0.001) and TIMP-1 (p = 0.002) were significantly lower in dogs with CHD compared to dogs with no CHD. ROC curve analyses were successful in establishing a panel of four biomarkers (urinary CTX-I and II, serum MMP-9, and serum PIICP) with high discriminatory capability for the presence or absence of hip dysplasia in adult dogs (AUC = 0.89). Urine and serum biomarkers can distinguish adult dogs with radiographic CHD from those with no CHD with a sensitivity of 0.95 and specificity of 0.77 using ROC analysis with AUC 0.89. Clinical Significance: This finding suggests that this simple, minimally invasive diagnostic technique has potential for discriminating dysplastic dogs from dogs with normal hips, with possible translational application to humans based on similar etiopathogenesis. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 9999:1-5, 2019.