Relationship between urinary sodium excretion and bone mineral density in pediatrics: population-based study from KNHANES V 2010-2011.

OBJECTIVES: Osteoporosis poses a growing public health challenge worldwide. While calcium and vitamin D may influence bone mineral density (BMD), the effect of sodium (Na) intake, particularly in pediatrics, remains unexplored. This study aimed to evaluate the relationship between urinary Na excretion and BMD in a Korean pediatric population. METHODS: A total of 2,018 participants (1,084 males and 934 females) aged 10-18 years were included from the data obtained from Korea National Health and Nutrition Examination Survey V (2010-2011). RESULTS: Daily Na intake was about 4,560 mg and 3,600 mg in boys and girls, respectively. The mean intake of Na per day was positively correlated with the increment of urine Na/Cr ratio quartile (p<0.001). The BMD z-score [lumbar spine (LS), femur neck (FN), and whole body except head (WB)] in the group with high Na/Cr ratio (4th quartile, 4Q) was significantly less than in those with low Na/Cr ratio (1st quartile, 1Q) (p<0.001). Moreover, the LS (p=0.028), FN (p=0.002) and WB (p=0.056) in the 4Q group showed 2.0 times, 2.8 times, and 1.9 times greater risk of low BMD z-scores than in the 1Q group, even after adjusting for other confounding factors, such as age, sex, BMI, vitamin D, moderate activity, and household incomes. CONCLUSIONS: Our findings suggest a strong negative association between urine Na excretion and BMD among Korean children and adolescents. The results underscore the importance of public health interventions targeting Na intake. Further longitudinal studies are recommended to clarify the long-term effects of Na on bone health in younger populations.

ATF5, a putative therapeutic target for the mitochondrial DNA 3243A > G mutation-related disease.

The mitochondrial DNA m.3243A > G mutation is well-known to cause a variety of clinical phenotypes, including diabetes, deafness, and osteoporosis. Here, we report isolation and expansion of urine-derived stem cells (USCs) from patients carrying the m.3243A > G mutation, which demonstrate bimodal heteroplasmy. USCs with high levels of m.3243A > G mutation displayed abnormal mitochondrial morphology and function, as well as elevated ATF5-dependent mitochondrial unfolded protein response (UPRmt), together with reduced Wnt/ß-catenin signaling and osteogenic potentials. Knockdown of ATF5 in mutant USCs suppressed UPRmt, improved mitochondrial function, restored expression of GSK3B and WNT7B, and rescued osteogenic potentials. These results suggest that ATF5-dependent UPRmt could be a core disease mechanism underlying mitochondrial dysfunction and osteoporosis related to the m.3243A > G mutation, and therefore could be a novel putative therapeutic target for this genetic disorder.

Retrospective analysis of the clinical characteristics of adefovir dipivoxil-induced Fanconi's syndrome in the Chinese population.

WHAT IS KNOWN AND OBJECTIVE: To explore the clinical characteristics of adefovir dipivoxil-induced Fanconi's syndrome in the Chinese population and provide a reference for rational drug use in the clinic. METHODS: By searching the CNKI, Wanfang, Chinese VIP, PubMed/MEDLINE, Web of Knowledge, Ovid, Elsevier and SpringerLink databases during 1 January 2008 to 31 December 2019, 78 studies of ADV-induced Fanconi's syndrome involving a total of 110 patients were collected and analysed retrospectively. RESULTS AND DISCUSSION: Prolonged usage of adefovir dipivoxil at low doses to treat hepatitis B might cause Fanconi's syndrome as the first symptom, especially for use over 12 months.The main clinical manifestation was bone pain accompanied by hypophosphataemia, elevated alkaline phosphatase (ALP), urine glycosuria and urine protein. X-rays and bone mineral density (BMD) examinations were mainly used to characterized osteoporosis. The patients had pain relief within 1 week to 1 month, and the biochemical indicators returned to normal within from 2 to 4 months. WHAT IS NEW AND CONCLUSION: Sufficient attention is required before and during exposure to long-term ADV therapy. The clinical picture, laboratory and radiograph alterations are important clues for ADV-induced Fanconi's syndrome.

Hyperparathyroidism in patients over 75: Clinical characteristics and outcome. Is conservative treatment a safe alternative?

OBJECTIVE: With the current aging of the world's population, primary hyperparathyroidism (PHPT) is increasingly detected in the elderly. Yet data on the presentation and outcome of PHPT in this group are scarce. The objective was to describe a cohort of patients aged 75 years or more with PHPT observed in our endocrine clinic. STUDY DESIGN: A retrospective analysis of medical records in an endocrine clinic at a tertiary hospital. We evaluated 182 patients with PHPT, aged 75 years or more at their last follow-up, all diagnosed at age 65 or more. Laboratory data were compared at diagnosis and last follow-up. RESULTS: Mean age at diagnosis was 73 ± 4 years, last follow-up was at 83 ± 4 years, and mean follow-up was 11.3 ± 5.5 years. Osteoporosis, fractures, and nephrolithiasis were diagnosed in 114(63 %), 84(46 %), and 43(24 %) patients, respectively. Overall, 150 patients had an indication for surgery; of them, the 29 who underwent parathyroidectomy were younger than the non-operated patients and had higher rates of hypercalciuria. During the follow-up of the 141 patients who did not undergo operation, serum and urinary calcium levels significantly had decreased, and vitamin D level had increased at last visit (10.4 ± 0.5 mg/dl, 161 ± 70 mg/24 h, 69 ± 17 nmol/l, p < 0.01 respectively) compared with levels at diagnosis (10.6 ± 0.2 mg/dl, 223 ± 95 mg/24 h, 53 ± 15 nmol/l, respectively, p = 0.001). Overall, 38 of the 182 patients (20 %) died during follow-up; these patients were significantly older at diagnosis (76 ± 5 vs. 72 ± 4 years) but there were no differences in laboratory variables. CONCLUSIONS: While most patients had a formal indication for surgery, few underwent parathyroidectomy. Serum and urinary calcium significantly decreased during follow-up in patients who did not undergo surgery. Our data are reassuring and support at least the consideration of conservative treatment for these patients.

Doxercalciferol Alleviates Bone Deteriorations and Cartilage Degeneration in Aging Mice.

BACKGROUND: Age-related bone deteriorations are the common endocrine disorders in the elderly population, leading to an increased risk of fractures. Therefore, effective treatment strategies provide a way to prevent bone loss and improve the quality of life in the elderly population. The present study aimed to investigate the anti-osteoporotic effects of doxercalciferol (DOX) in aging mice. METHODS: Bone metabolism-related markers were measured by ELISA assay. The expression of bone formation and resorption-related genes was performed by RT-qPCR analysis. Hematoxylin and eosin (H&E) and Safranin O staining were performed to analyze the trabecular bone and cartilage degeneration. RESULTS: Aging resulted in urine ca2+ excretion, a decrease in bone ca2+ content and reduction of biomechanical strength in mice. We also found that the level of PTH was increased in aging mice, while DOX administration markedly down-regulated serum PTH in aging mice. H&E and Safranin O staining showed that DOX protected against aging-induced bone loss and cartilage regeneration in the tibia from aging mice. Furthermore, DOX treatment resulted in an increase in Runx2, osterix and Col1a1 mRNA expression and a decrease in Ctsk, MMP-9 and CAII mRNA expression in the tibia from aging mice. CONCLUSION: These findings indicated that DOX had a beneficial effect on age-related bone deteriorations in aging mice by promoting osteoblast activity and cartilage regeneration and inhibiting osteoclast-specific genes expression.

Possible osteoprotective effects of myricetin in STZ induced diabetic osteoporosis in rats.

Myricetin is a flavonoid which has many pharmacological effects. However, to date there is no evidence study on the effect of myricetin in diabetic condition. This study was aimed to investigate whether myricetin could protect against diabetic osteoporosis in streptozotocin induced rats. Female Wistar rats were randomly allocated to four equal groups: diabetic group (DG), diabetic group with myricetin (50 mg per kilogram per day), (D) diabetic group with myricetin (100 mg/kg/day) and normal control group (CG). Body weight was recorded once a week. After treatment with myricetin for 12 weeks, serum biochemical analyses, the microarchitecture of femora, and histological changes were evaluated. We found that the bone mineral density (BMD) of myricetin (100 mg per kilogram per day)treatment group significantly increased than in the diabetic group (P < 0.05). The alkaline phosphatase and osteocalcin were markedly blocked in diabetic rats relative to normal control group (P < 0.05); however, the inhibition was prevented by the myricetin treatment group. Results also showed that myricetin treatment could dramatically improve trabecular bone microarchitecture through increasing bone mass such as trabecular number (Tb.N), bone volume per tissue volume (BV/TV), and decreasing that of structure model index (SMI) and trabecular separation (Tb.Sp), comparing with the control group. We also found that myricetin could significantly lower the oxidative damage and up-regulate the activity of superoxide dismutase (SOD) and catalase activity. In summary, we showed that myricetin can effectively improve abnormal bone metabolism in streptozotocin induced rats, which may provide a beneficial medicine on diabetic bone disease.

Co-exposure of cadmium and lead on bone health in a southwestern Chinese population aged 40-75 years.

Both cadmium (Cd) and lead (Pb) are associated with bone health, but studies exploring the effects of Cd and Pb co-exposure on bone health are rare. This study aimed to assess the interactive effects of Cd and Pb co-exposure on bone health. In total, 799 participants, living in the targeted areas (located in southwestern China) for more than 15 years, aged 40-75 years, and subsisted on homegrown rice and vegetables were investigated. Cd and Pb levels in urine and blood samples, as well as bone mineral density, T- and Z-score were determined. After being adjusted for covariates, the T-score was negatively correlated with blood Pb in men (P < .05); for women and non-smoking women, the T-score was negatively correlated with urinary Pb (P < .05). Moreover, after being adjusted for covariates, the Z-score was negatively correlated with urinary Pb in non-smoking women (P < .05). No positive association of prevalence of osteoporosis with Cd and Pb exposure was found. However, at an additive scale, positive interactions of urinary Cd and Pb on the prevalence of osteoporosis for women and non-smoking women, and the same interactions to blood Cd and Pb for men were found. There was also a positive interaction of urinary Cd and Pb for women at a multiplicative scale. This study suggests Cd and Pb exposure could exert detrimental effects on bone health, with possible underlying interactions. Nevertheless, more studies are needed to explore the interactive effects of heavy metal co-exposure.

Non-invasive skin autofluorescence, blood and urine assays of the advanced glycation end product (AGE) pentosidine as an indirect indicator of AGE content in human bone.

BACKGROUND: Bone mineral density (BMD) measurements are widely used to assess fracture risk. However, the finding that some fracture patients had high BMD together with the low contribution of drugs to osteoporosis suggests that bone strength factors other than BMD contribute to bone quality. We evaluated the amount of advanced glycation end products (AGEs) by non-invasive assays of serum and urine as well as by skin autofluorescence to measure the levels of a representative AGE, pentosidine, to investigate whether pentosidine can serve as an indirect indicator of AGEs formation in bone collagen. METHODS: A total of 100 spinal surgery patients without fragility fracture (54 males and 46 females) treated at our hospital were enrolled. The amount of pentosidine in blood, urine, skin and bone (lumbar lamina) samples from these patients was measured. AGE accumulation was assessed by measuring skin autofluorescence. We examined the correlation between pentosidine content in tissues and body fluid, as well as skin AGEs with age, height, body weight, BMI, and estimated glomerular filtration rate (eGFR). RESULTS: A significant age-related increase in pentosidine levels in tissues was observed, while there was a significant negative correlation between tissue pentosidine and eGFR. The amount of skin pentosidine was significantly and positively correlated with pentosidine content of the bone in those under 50 years of age. Urine pentosidine also correlated positively with bone pentosidine and skin pentosidine, but only in females. The total amount of AGEs in skin did not correlate with bone pentosidine. CONCLUSION: In this study, the strong correlation between the pentosidine content in each sample and eGFR may indicate that renal dysfunction with advancing age increases oxidative stress and induces AGEs formation in collagen-containing tissues. The correlation of skin pentosidine concentration and eGFR, with AGEs formation in bone collagen suggests that pentosidine would be a useful indirect index of decreased bone quality. Skin AGEs estimated by autofluorescence in clinical situations may not be suitable as an indirect assessment of bone quality. Because urine pentosidine correlated positively with bone pentosidine and skin pentosidine in females, urine pentosidine may be a candidate for an indirect assessment of bone quality.

Denosumab Improves Glomerular Filtration Rate in Osteoporotic Patients With Normal Kidney Function by Lowering Serum Phosphorus.

Higher serum phosphorus (Pi) increases the risk for chronic kidney disease (CKD). It was reported that a single administration of denosumab or zoledronate significantly suppressed serum Pi levels as well as those of bone resorption markers in serum. Also, previous evidences suggest a link between bone anti-resorptive therapy and vasoprotective/renoprotective effects through mechanisms that remain unexplored. The aim of this study is to assess the renoprotective effect of denosumab and involvement of denosumab-induced reduction in serum Pi in osteoporotic patients. Osteoporotic patients (n = 73) without overt proteinuria in dipstick test results were treated with denosumab (60 mg) every 6 months during the study period (24 months). Estimated glomerular filtration rate based on serum cystatin C (eGFRcys) was used as a filtration marker and tartrate-resistant acid phosphatase-5b (TRACP-5b) as a bone resorption marker. For analysis of non-CKD patients (n = 56), those with eGFRcys <60 mL/min/1.73 m2 were excluded. A single injection of denosumab suppressed serum Pi as well as TRACP-5b during the first 6 months, whereas age-related decline in eGFRcys was significantly reversed, with an increase of 2.75 ± 1.2 mL/min/1.73 m2 after 24 months noted. Multivariate analysis showed that serum Pi reduction following the initial denosumab injection was positively associated with serum TRACP-5b suppression during that same period (ß = 0.241, p = 0.049). In addition, a positive association of serum Pi suppression, but not of corrected calcium or TRACP-5b, with eGFRcys increase after 24 months (ß = 0.321, p = 0.014) was found after adjustments for gender, age, BMI, antihypertensive drug use, albumin, and eGFRcys. The same was observed in osteoporotic cases restricted to non-CKD patients. In conclusion, serum Pi reduction resulting from phosphorus load decrement from bone induced by denosumab is a determinant for eGFRcys increase. Early introduction of bone antiresorptive therapy can retain glomerular filtration in osteoporosis cases, including non-CKD patients. © 2019 American Society for Bone and Mineral Research.

Eldecalcitol increases bone mineral density in Chinese osteoporotic patients without vitamin D or calcium supplementation.

Eldecalcitol increased bone mineral density (BMD) and prevented vertebral fractures in vitamin D-sufficient osteoporotic subjects. However, the effect of eldecalcitol on BMD under vitamin D insufficiency is unknown. We examined the effect of eldecalcitol on BMD compared with alfacalcidol in osteoporotic patients without vitamin D or calcium supplementation. This is a randomized, double-blind, active comparator trial. 265 Chinese osteoporotic patients were randomly assigned to receive 0.75 µg eldecalcitol or 1.0 µg alfacalcidol for 12 months without vitamin D or calcium supplementation. Baseline calcium intakes were less than 550 mg/day and mean serum 25-hydroxyvitamin D [25(OH)D] was below 43 nmol/L in both groups. Baseline BMD tended to be lower in patients with lower calcium intake and serum 25(OH)D. Lumbar BMD increased by 2.05% higher in eldecalcitol than alfacalcidol group at 12 months. Total hip and femoral neck BMD also increased by 1.33 and 1.78%, respectively, in the eldecalcitol than the alfacalcidol group. The effect of eldecalcitol on BMD was not affected by serum 25(OH)D or calcium intake. The incidence of adverse events was not different between the two groups. Incidence of hypercalcemia in the edecalcitol group was not affected by serum 25(OH)D. In conclusion, baseline BMD tended to be lower in patients with low calcium intake and serum 25(OH)D. Eldecalcitol increased lumbar and hip BMD more than alfacalcidol regardless of serum 25(OH)D or calcium intake without vitamin D or calcium supplementation. These results suggest that eldecalcitol is effective in increasing the BMD of osteoporotic patients regardless of vitamin D status or calcium intake.Clinical Trial Registration number JAPIC CTI 152904.

Exercise Alleviates Osteoporosis in Rats with Mild Chronic Kidney Disease by Decreasing Sclerostin Production.

Chronic kidney disease-mineral bone disorder (CKD-MBD), comprising mineral, hormonal, and bone metabolic imbalance, is a major CKD-related issue; it causes osteoporosis prevalence in CKD patients. Osteocyte-derived sclerostin inhibits the osteogenic Wnt/ß-catenin signaling pathway; its levels rise when kidney function declines. Exercise modulates the physiological functions of osteocytes, potentially altering sclerostin production. It may aid bone and mineral electrolyte homeostasis in CKD. Mild CKD was induced in rats by partial nephrectomy. They were divided into: sham (no CKD), CKD, and CKD + exercise (8 weeks of treadmill running) groups. Micro-CT scanning demonstrated that the CKD + exercise-group rats had a higher bone mineral density (BMD) of the spine and femoral metaphysis and higher femoral trabecular bone volume than the CKD-group rats. Bone formation rates were not significantly different. The CKD + exercise-group rats had lower serum sclerostin (157.1 ± 21.1 vs 309 ± 38.1 pg/mL, p < 0.05) and CTX-1 (bone resorption marker) levels. Immunohistochemistry revealed higher tibial ß-catenin concentrations in the CKD + exercise-group rats. Serum FGF-23, intact parathyroid hormone (iPTH), alkaline phosphatase (ALP), calcium, and phosphate levels showed no significant differences between these groups. Thus, exercise improves BMD and bone microstructure in mild CKD by inhibiting sclerostin production, but does not alter serum minerals.

Effectiveness of thiazides on serum and urinary calcium levels and bone mineral density in patients with osteoporosis: a systematic review and meta-analysis.

OBJECTIVE: Osteoporosis is the most common metabolic bone disease and a major public health problem worldwide. Thiazides are widely used as antihypertensive agents with good tolerability and efficacy. Furthermore, thiazides have long been regarded as candidates for the prevention of postmenopausal bone loss. However, there is insufficient evidence that thiazides have a sustained beneficial effect on preserving bone mass and preventing osteoporosis to date. MATERIALS AND METHODS: We searched the PubMed, the Cochrane Library, and Embase in June 2018 for randomized controlled trials on the use of thiazides to treat osteoporosis. Continuous outcomes are presented as the standardized mean difference (SMD) and 95% CI. Furthermore, P-values <0.05 were considered significant. RESULTS: Five trials with 756 patients were randomly assigned in the five trials included in this meta-analysis. Serum calcium level was higher in the thiazide group than in the control group (SMD 0.33, 95% CI [0.16, 0.50]), and urinary calcium level was significantly lower in the thiazide group (SMD -0.35, 95% CI [-0.52, -0.17]). There was no significant difference in bone mineral density between the two groups (SMD 0.19, 95% CI [-0.16, 0.54]). CONCLUSION: Thiazides might play a role in preserving bone mass and be effective in the prevention and treatment of osteoporosis. Future high-quality trials are needed to confirm our findings in the future.

Correlation analysis of urine proteins and inflammatory cytokines with osteoporosis in patients with diabetic nephropathy.

OBJECTIVES: To analyze the relationship of urine proteins and inflammatory cytokines with osteoporosis in patients with diabetic nephropathy. METHODS: 76 patients with diabetic nephropathy in Xintai Affiliated Hospital of Taishan Medical University were selected and divided into the combination with osteoporosis group (n=28) and the non-combination with osteoporosis group (n=48). The general data of patients was collected, and T scores of lumbar vertebrae and hips of the patients were recorded. RESULTS: Duration of diabetes mellitus (DM) and levels of glycosylated hemoglobin A1c (HbA1c), fasting plasma glucose (FPG) and fasting insulin (FINS) level, levels of C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-α) and interleukin 6 (IL-6), level of 24h urine protein (24hndb) of patients in the combination with osteoporosis group was significantly higher, while the value of eGFR was lower than that of patients in the non-combination with osteoporosis group. The bone mineral densities (BMDs) and T scores of lumbar vertebrae and hips of patients in the combination with osteoporosis group were statistically significantly lower than those of patients in the non-combination with osteoporosis group. 24hndb, CRP, TNF-α and IL-6 were all negatively correlated with BMD. Duration of DM, FPG, HbA1c, FINS, 24hndb, BMD and inflammatory cytokines had independent predictive values for patients with diabetic nephropathy combined with osteoporosis. CONCLUSION: 24hndb and inflammatory cytokines are closely related to the combination with osteoporosis in patients with diabetic nephropathy.

[Characteristic features of urinary calcium excretion and osteoporosis risk factors in patients with urolithiasis].

RELEVANCE: The prevalence of urolithiasis and osteoporosis (OP) indicates that these diseases may be found concurrently in the same patient. The detection of risk factors for OP and disorders of calcium metabolism in patients with urolithiasis is of interest in the context of primary stone formation and metaphylaxis. AIM: To identify risk factors for osteoporosis and disorders of calcium metabolism in patients with urolithiasis. MATERIALS AND METHODS: Osteoporosis risk factors were studied in 45 urolithiasis patients undergoing surgical treatment. Patients were asked to fill out the osteoporosis risk factor questionnaire, and urinary calcium excretion was measured in 24-h collections. RESULTS: Risk factors for osteoporosis were detected in 20 (44.4%) urolithiasis patients. Patients with osteoporosis risk factors identified by the questionnaire were statistically significantly older (p=0.032). Osteoporosis risk factors were found in 20% of patients with newly diagnosed urolithiasis and 24.4% of patients with recurrent urolithiasis. The study patients showed increased urinary calcium excretion and decreased diuresis. The negative correlation between urinary calcium excretion and 24-h diuresis was greater in patients who had than in those who did not have osteoporosis. CONCLUSION: An increase in urinary calcium excretion and a decrease in diuresis can be a predisposing factor for the recurrence of urolithiasis. In patients with risk factors for osteoporosis, it can provide a rationale for administering drugs aimed at preventing stone formation (thiazide diuretics).

Clinical utility of bone markers in various diseases.

Measurements of bone markers (BMs) in peripheral blood or urine are a pivotal part of bone research within modern clinical medicine. In recent years the use of BMs increased substantially as they can be useful either to diagnose bone (related) disease and to follow its natural history, but also to monitor the effects of interventions. However, the use of BMs is still complicated mainly due to (pre)analytical variability of these substances, limited accessibility of assays, variable cut-off values in different countries and laboratories and heterogeneous results with regard to clinical implications of measuring BMs in several studies. This review will provide the clinician with a practical guide, based on current evidence, in which circumstances to test which bone markers for optimal diagnostic purposes, in order to improve patient care in different areas of bone diseases including Paget's disease, primary osteoporosis, tumor induced osteomalacia, hypophosphatemic rickets, van Buchem disease, chronic kidney disease, rheumatoid arthritis, neoplasma/multiple myeloma, type 2 diabetes mellitus and primary hyperparathyroidism. The clinician should consider fasting state, recent fractures, aging, menopausal status, concomitant liver and kidney disease when ordering and interpreting BM measurements as these factors might result in misleading BM concentrations. We found that BMs are clearly useful in the current diagnosis of tumor induced osteomalacia, van Buchem disease, Paget's disease and hypophosphatemic rickets. In addition, BMs are useful to monitor disease activity in chronic kidney disease, Paget's disease and are useful to monitor treatment adherence in osteoporosis.

The phytoestrogen genistein prevents trabecular bone loss and affects thyroid follicular cells in a male rat model of osteoporosis.

As a major phytoestrogen of soy, genistein effectively prevents bone loss in both humans and rat models of osteoporosis. However, although the bone-sparing effects of genistein are achieved directly through estrogen receptors, its mode of action on bone by modulation of other endocrine functions is not entirely clear. Thus, thyroid hormones and calcitonin (CT) have an essential influence on bone metabolism. Besides its action on bones, in this study we examined the effect of genistein on the activity of two different endocrine cell populations, thyroid follicular and C-cells. Fifteen-month-old Wistar rats were either bilaterally orchidectomized (Orx) or sham-operated (SO). Two weeks after surgery, half of the Orx rats were treated chronically with 30 mg kg-1 b.w. genistein (Orx + G) subcutaneously (s.c.) every day for 3 weeks, while the remaining Orx rats and the SO rats were given the same volume of sterile olive oil to serve as controls. For histomorphometrical analysis of the trabecular bone microarchitecture an ImageJ public domain image processing programme was used. Thyroid sections were analysed histologically and stereologically after visualization of follicular and C-cells by immunohistochemical staining for thyroglobulin and CT. Thyroid follicular epithelium, interstitium, colloid and CT-immunopositive C-cells were examined morphometrically. Serum concentrations of osteocalcin (OC), triiodothyronine (T3 ), thyroxine (T4 ) and CT were determined as well as urinary calcium (Ca2+ ) concentrations. Genistein treatment significantly increased cancellous bone area (B.Ar), trabecular thickness (TbTh) and trabecular number (TbN) (P < 0.05), but trabecular separation (Tb.Sp) was decreased (P < 0.05) compared with control Orx rats. In the thyroid, genistein treatment significantly elevated the relative volume density (Vv) of the follicular cells (P < 0.05) compared with Orx, whereas Vv of the colloid was lower (P < 0.05) than in the Orx. Evaluation of the biochemical parameters showed significant reductions in serum OC, T3 , T4 and urinary Ca2+ concentrations (P < 0.05), compared with Orx rats. These data indicate that genistein treatment improves the trabecular microarchitecture of proximal tibia, induces histomorphometrical changes in thyroid glands, and decreases circulating thyroid hormone levels in orchidectomized rat model of male osteoporosis.

Risk of renal stone formation in patients treated with luteinising hormone-releasing hormone analogues for prostate cancer: importance of bone metabolism and urine calcium.

PURPOSE: To determine whether androgen blockade produces metabolic changes in urine and increases the risk of calculi after 1 year of treatment. MATERIALS AND METHODS: The study included 38 patients, from the period April 2015 to June 2016, diagnosed with locally advanced prostate cancer or lymph node metastasis, and with an indication of androgen blockade. Androgen blockade was started with luteinising hormone-releasing hormone (LHRH) analogues, and a blood specimen, a fasting urine and 24-h urine were collected at the time of inclusion, and then at 1 year of follow-up. A study was performed at baseline and at 1 year with imaging tests. An analysis of the variables was performed with a p ≤ 0.05 considered as statistically significant. RESULTS: The mean age of the patients included in the study was 72.26 ± 6.75 years. As regards the biochemistry parameters, an increase in osteocalcin (from 16.28 ± 9.48 to 25.56 ± 12.09 ng/ml; p = 0.001) and an increase in ß-crosslaps (from 0.419 ± 0.177 to 0.743 ± 0.268 ng/ml; p = 0.0001) were observed. In the urinary parameters, a significant increase was observed in the fasting calcium/creatinine ratio (from 0.08 ± 0.06 to 0.13 ± 0.06; p = 0.002) and in the 24-h calcium renal excretion (from 117.69 ± 66.92 to 169.42 ± 107.18 mg; p = 0.0001). Calculi formation was observed in 12 of the 38 patients included (31.6%), with a mean size of 3.33 ± 1.31 mm. CONCLUSION: Treatment with LHRH analogues, as well as increasing the appearance of metabolic syndrome and speeding up the loss bone mineral density, causes an increase in fasting urine calcium.

Urinary Bone Turnover Markers as Target Indicators for Monitoring Bisphosphonate Drug Treatment in the Management of Osteoporosis.

BACKGROUND: Osteoporosis is a debilitating disease characterized by bone micro-architecture degradation contributing to fragility fractures. Currently, determining bone mineral density (BMD) via dual-energy X-ray absorptiometry (DXA) is the most reliable form of diagnosing osteoporosis and managing pharmacological treatment regimens. However, changes in BMD occur slowly (i.e., several months) and DXA does not reflect the metabolic rate of bone turnover. Alternatively, biochemical bone turnover markers are metabolic indicators released into serum and/or urine, and their quantity reflects the metabolic activity of bone. bone turnover markers show a rapid response following antiresorptive drug administration, and enzyme-linked immunosorbent assays (ELISA) have been established and used in clinical trials to help assess and predict fracture risk independent of BMD. OBJECTIVE: This review highlights various established bone turnover markers that have found utility in the clinic as reliable and standardized indicators of bone turnover, with attention to those used to assess efficacy of bisphosphonate drug therapy - particularly in monitoring medication adherence in patients with postmenopausal osteoporosis. RESULTS: We posit that the use of urinary bone turnover markers values determined by immunoassay or ELISA at routine clinic visits might serve as valuable feedback to healthcare professionals and patients to help monitor the efficacy and adherence of bisphosphonate therapy and disease progression. CONCLUSION: Our belief is that when assessed in combination with an algorithm of independent risk factors, measuring urinary bone turnover markers using a point of care kit may find utility in the osteoporosis clinic as an accessible, non-invasive and cost-effective alternative for the routine assessment of efficacy of bisphosphonate therapies.

Cadmium Exposure and Osteoporosis: A Population-Based Study and Benchmark Dose Estimation in Southern China.

This study aimed to assess the association between osteoporosis and long-term environmental Cd exposure through diet in southern China. A total of 1116 subjects from a Cd-polluted area and a non-Cd-polluted area were investigated. All subjects met the criteria of having been living in the investigated area for more than 15 years and lived on a subsistence diet of rice and vegetables grown in that area. Besides bone mineral density, the levels of urinary markers of early renal impairment, such as urinary N-acetyl-ß-D-glucosaminidase (NAG), α1 -microglobulin, ß2 -microglobulin, and urinary albumin, were also determined. Urinary Cd concentrations of all studied subjects ranged from 0.21 to 87.31 µg/g creatinine, with a median of 3.97 µg/g creatinine. Multivariate linear regression models indicated a significant negative association of urinary Cd concentrations with bone mineral density. In logistic regression models, both categorical and continuous urinary Cd concentrations were positively associated with osteoporosis. Subjects in the second, third, and fourth quartiles of urinary Cd concentration had greater odds of osteoporosis compared with subjects in the first quartile (odds ratio [OR] = 3.07, 95% confidence interval [CI], 1.77 to 5.33; OR = 4.63, 95% CI, 2.68 to 7.98; OR = 9.15, 95% CI, 5.26 to 15.94, respectively). Additional adjustment for levels of urinary markers did not attenuate the associations. No evidence existed of an interaction between urinary Cd concentration and renal function using levels of urinary markers, and estimated glomerular filtration rate (eGFR). In all subjects, the benchmark dose and benchmark dose lower bound were 1.14 (0.61) and 2.73 (1.83) µg/g creatinine, with benchmark response set at 5% and 10%, respectively. The benchmark dose of urinary Cd was lower in women than in men. This study demonstrated an inverse association between the body burden of Cd and osteoporosis. The toxic effect of Cd on bone may occur in parallel to nephrotoxicity. © 2017 American Society for Bone and Mineral Research.

Changes in Bone Mineral Density, Body Composition, Vitamin D Status, and Mineral Metabolism in Urban HIV-Positive South African Women Over 12 Months.

Human immunodeficiency virus (HIV) infection and antiretroviral therapy (ART) are associated with bone loss and poor vitamin D status in white populations, though their relative roles are not known. No previous studies have examined longitudinal changes in areal bone mineral density (aBMD), measured by dual-energy X-ray absorptiometry (DXA), or in vitamin D status in HIV-positive African women. Of 247 premenopausal, urban, black African women from Soweto, South Africa, initially recruited, 187 underwent anthropometry, DXA scanning and blood and urine collections at both baseline and 12 months. Of these, 67 were HIV-negative throughout (Nref), 60 were HIV-positive with preserved CD4 counts at baseline (Ppres), and 60 were HIV-positive with low CD4 counts at baseline, eligible for ART by South African standards of care at the time (Plow). No participant had been exposed to ART at baseline. By 12 months, 51 Plow women had initiated ART, >85% of whom took combined tenofovir disoproxil fumarate (TDF), lamivudine, and efavirenz. By 12 months, Plow and Nref, but not Ppres, increased in body weight and fat mass (group-by-timepoint p ≤ 0.001, p = 0.002, respectively). Plow had significant decreases in aBMD of 2% to 3%, before and after size adjustment, at the femoral neck (p ≤ 0.002) and lumbar spine (p ≤ 0.001), despite significant weight gain. These decreases were associated with increased bone turnover but there were no significant differences or changes over time in vitamin D status, serum phosphate concentrations, or renal phosphate handling. Excluding data from nine Plow women unexposed to ART and 11 Ppres women who had initiated ART accentuated these findings, suggesting the bone loss in Plow was related to ART exposure. This is the first study describing DXA-defined bone loss in HIV-positive Sub-Saharan African women in association with ART. Further work is required to establish if bone loss continues with ongoing ART and, if so, whether this results in increased fracture rates. © 2017 American Society for Bone and Mineral Research.