Serum Bone-specific Alkaline Phosphatase Research Articles

Effects of minodronate in postmenopausal women with osteoporosis who received prior treatment with raloxifene.

BackgroundIn clinical practice, patients with postmenopausal osteoporosis have often shown a poor response to treatment with an antiresorptive agent for several years. The purpose of this study was to investigate the efficacy of switching raloxifene with minodronate in patients who responded poorly to the treatment of postmenopausal osteoporosis with raloxifene.Patients and methodsThis observational study was conducted based on a single-arm, non-randomized, open-label design and was approved by the institute’s institutional review board. Postmenopausal women with osteoporosis who became unresponsive in terms of bone mineral density (BMD) after being administered raloxifene for two or more years were enrolled. Patients were treated with 1 mg minodronate daily or 50 mg minodronate monthly. Changes in BMD and serum bone turnover markers were monitored at baseline, 6, 12, and 24 months after switching treatment.ResultsTwenty-seven patients were enrolled. Two discontinued treatment because of adverse events related to the study drug. Among the remaining 25 patients, lumbar BMD significantly increased by 3.67%, 5.08%, and 6.97% at 6, 12, and 24 months, respectively, and femoral neck BMD increased by 1.63%, 2.18%, and 3.85% at 6, 12, and 24 months, respectively. Serum bone-specific alkaline phosphatase showed a significant reduction of 30.35% from the baseline (p<0.0001) within the first 6 months, suggesting a stronger antiresorptive effect of minodronate. Serum N-terminal telopeptide of type I collagen showed a tendency to decrease.ConclusionSwitching raloxifene with minodronate is effective in poor responders of osteoporosis treatment and should be considered as one of the treatment options for osteoporosis.

The Effect of Vitamin D Supplementation on Bone Metabolic Markers in Chronic Kidney Disease.

Use of active forms of vitamin D is advocated in patients with chronic kidney disease (CKD) for treatment of mineral bone disease because of the presumption that native forms of vitamin D would not undergo significant activation to calcitriol, the most active biological form of vitamin D. We present secondary analysis looking at bone turnover in subjects who completed the randomized, double blind, placebo-controlled trial investigating the effect of cholecalciferol supplementation on vascular function in nondiabetic CKD stage G3-G4 and vitamin D ≤20 ng/mL (Clinical Trials Registry of India: CTRI/2013/05/003648). Patients were randomized (1:1) to receive either two directly observed oral doses of 300,000 IU of cholecalciferol or matching placebo at baseline and 8 weeks. Of the 120 subjects enrolled, 58 in the cholecalciferol group and 59 in the placebo group completed the study. At 16 weeks, the serum 25(OH)D and 1,25(OH)2 D levels increased in the cholecalciferol group but not in the placebo group (between-group difference in mean change: 23.40 ng/mL; 95% CI, 19.76 to 27.06; p < 0.001, and 14.98 pg/mL; 95% CI, 4.48 to 27.18; p = 0.007, respectively). Intact parathyroid hormone (iPTH) decreased in the cholecalciferol group (between-group difference in mean change -100.73 pg/mL (95% CI, -150.50 to -50.95; p < 0.001). Serum total and bone-specific alkaline phosphatase (SAP, BAP) and serum C-terminal cross-linked collagen type I telopeptides (CTX-1) were significantly reduced in cholecalciferol group (between group difference for change in mean: -20.25 U/L; 95% CI, -35.14 to -5.38 U/L; p = 0.008 for SAP; -12.54 U/L; 95% CI, -22.09 to -2.98 U/L; p = 0.013 for BAP; and -0.21 ng/mL; 95% CI, -0.38 to -0.05 ng/mL; p = 0.05 for CTX-1). Correlation analysis showed significant correlation of Δ25(OH)D with ΔiPTH (r = -0.409, p < 0.0001), Δ1,25(OH)2 D (r = 0.305, p = 0.001), ΔSAP (r = -0.301, p = 0.002), ΔBAP (r = -0.264, p = 0.004), and ΔCTX-1 (r = -0.210, p = 0.0230). Cholecalciferol supplementation corrects vitamin D deficiency and is effective in lowering serum intact parathyroid hormone and bone turnover markers in early stages of CKD. © 2017 American Society for Bone and Mineral Research.

Do acid suppressive drugs (pantoprazole and ranitidine) attenuate the protective effect of alendronate in estrogen-deficient osteoporotic rats?

BackgroundAlendronate is a drug of choice in the treatment of postmenopausal osteoporosis. Acid suppressive drugs are recently used in combination with alendronate to protect against stomach ulceration and oesophagitis occurring as serious problems in patients under this treatment. Aim of the workTo study the effect of pantoprazole and ranitidine on the anti-resorptive effect of alendronate in a rat model of osteoporosis. Material and methods64 female Wister albino rats were included (8 rats/group). Treated groups were Ovariectomized bilaterally to induce osteoporosis. Rats were treated orally with alendronate (3mg/kg/day), ranitidine (20mg/kg/day), pantoprazole (3mg/kg/day), combined alendronate and ranitidine or alendronate and pantoprazole for 4weeks. Bone mineral density (BMD) was determined using dual-energy X-ray absorptiometry scan. Serum bone-specific alkaline phosphatase (BSALP), serum calcium, cortical thickness and histopathological examination were assessed. ResultsInduction of osteoporosis significantly elevated serum BSALP, decreased serum calcium, bone mineral density and cortical thickness and significantly increased the histopathological score. Ranitidine treatment resulted in insignificant changes in tested parameters. Pantoprazole given alone, significantly decreased serum calcium and increased serum BSALP. At the end of the experiment, alendronate significantly improved BSALP level, serum calcium, BMD, cortical thickness and histopathological score. This improvement was not affected by combining ranitidine with alendronate. Meanwhile, pantoprazole with alendronate caused a significant deterioration of tested parameters. ConclusionRanitidine proved safer than pantoprazole for patients with high risk of osteoporosis and in alendronate-treated patients. Clinicians should carefully judge the indication of use of acid suppressing medications in osteoporotic patients.

Effect of low-magnitude different-frequency whole-body vibration on subchondral trabecular bone microarchitecture, cartilage degradation, bone/cartilage turnover, and joint pain in rabbits with knee osteoarthritis

BackgroudWhole-body vibration(WBV) has been suggested for the prevention of subchondral bone loss of knee osteoarthritis (OA) . This study examined the effects of different frequency of whole-body vibration on subchondral trabecular bone microarchitecture, cartilage degradation and metabolism of the tibia and femoral condyle bone, and joint pain in an anterior cruciate ligament transection (ACLT)–induced knee osteoarthritisrabbit model.MethodNinety adult rabbits were divided into six groups: all groups received unilateral ACLT; Group 1, ACLT only; Group 2, 5 Hz WBV; Group 3, 10 Hz WBV; Group 4, 20 Hz WBV; Group 5, 30 Hz WBV; and Group 6, 40 Hz WBV. Pain was tested via weight-bearing asymmetry. Subchondral trabecular bone microarchitecture was examined using in vivo micro-computed tomography. Knee joint cartilage was evaluated by gross morphology, histology, and ECM gene expression level (aggrecan and type II collagen [CTX-II]). Serum bone-specific alkaline phosphatase, N-mid OC, cartilage oligometric protein, CPII, type I collagen, PIIANP, G1/G2 aggrecan levels, and urinary CTX-II were analyzed.ResultsAfter 8 weeks of low-magnitude WBV, the lower frequency (10 Hz and 20 Hz) WBV treatment decreased joint pain and cartilage resorption, accelerated cartilage formation, delayed cartilage degradation especially at the 20 Hz regimen. However, the higher frequencies (30 Hz and 40 Hz) had worse effects, with worse limb function and cartilage volume as well as higher histological scores and cartilage resorption. In contrast, both prevented loss of trabeculae and increased bone turnover. No significant change was observed in the 5 Hz WBV group.ConclusionOur data demonstrate that the lower frequencies (10 Hz and 20 Hz) of low-magnitude WBV increased bone turnover, delayed cartilage degeneration, and caused a significant functional change of the OA-affected limb in ACLT-induced OA rabbit model but did not reverse OA progression after 8 weeks of treatment.

Two-year clinical outcome of denosumab treatment alone and in combination with teriparatide in Japanese treatment-naive postmenopausal osteoporotic women

This randomized prospective study aimed to evaluate the clinical outcome of denosumab treatment alone and in combination with teriparatide in treatment-naive postmenopausal Japanese female patients with osteoporosis. Thirty patients were randomly assigned to two groups: (1) denosumab group (denosumab alone, n=13); and (2) combination group (denosumab+teriparatide, n=17). Serum bone-specific alkaline phosphatase (BAP), serum tartrate-resistant acid phosphatase (TRACP)-5b, urinary cross-linked N-terminal telopeptides of type I collagen (NTX), and bone mineral density (BMD) of L1–4 lumbar vertebrae (L-BMD) and bilateral total hips (H-BMD) were determined at the first visit and at various time points up to 24 months post-treatment to determine percentage changes. Serum TRACP-5b and urinary NTX were equally suppressed in both groups and maintained at low levels, with slight increases at 12, 18 and 24 months. BAP was significantly decreased in both groups from 4 to 24 months, with significant differences between the groups at 4, 8 and 15 months (P<0.05). L-BMD was significantly increased at most time points in both groups, with a significant difference between the combination group and denosumab group at 24 months (17.2% increase versus 9.6% increase; P<0.05). There was no significant difference in H-BMD between the two groups, although the levels tended to be higher in the combination group than in the denosumab group (9.5% increase versus 5.6% increase). These findings suggest that denosumab+teriparatide combination therapy may represent an important treatment for primary osteoporotic patients at high risk of vertebral fracture.

Lower Bone Mass and Higher Bone Resorption in Pheochromocytoma: Importance of Sympathetic Activity on Human Bone.

Despite the apparent biological importance of sympathetic activity on bone metabolism in rodents, its role in humans remains questionable. To clarify the link between the sympathetic nervous system and the skeleton in humans. Among 620 consecutive subjects with newly diagnosed adrenal incidentaloma, 31 patients with histologically confirmed pheochromocytoma (a catecholamine-secreting neuroendocrine tumor) and 280 patients with nonfunctional adrenal incidentaloma were defined as cases and controls, respectively. After adjustment for confounders, subjects with pheochromocytoma had 7.2% lower bone mass at the lumbar spine and 33.5% higher serum C-terminal telopeptide of type 1 collagen (CTX) than those without pheochromocytoma (P = 0.016 and 0.001, respectively), whereas there were no statistical differences between groups in bone mineral density (BMD) at the femur neck and total hip and in serum bone-specific alkaline phosphatase (BSALP) level. The odds ratio (OR) for lower BMD at the lumbar spine in the presence of pheochromocytoma was 3.31 (95% confidence interval, 1.23 to 8.56). However, the ORs for lower BMD at the femur neck and total hip did not differ according to the presence of pheochromocytoma. Serum CTX level decreased by 35.2% after adrenalectomy in patients with pheochromocytoma, whereas serum BSALP level did not change significantly. This study provides clinical evidence showing that sympathetic overstimulation in pheochromocytoma can contribute to adverse effects on human bone through the increase of bone loss (especially in trabecular bone), as well as bone resorption.

Bone turnover and periprosthetic bone loss after cementless total hip arthroplasty can be restored by zoledronic acid: a prospective, randomized, open-label, controlled trial

BackgroundAlthough the loss of bone mineral density (BMD) after total hip arthroplasty (THA) is a known problem, it remains unresolved. This study prospectively examined the effect of zoledronic acid (ZA) on bone turnover and BMD after cementless THA.MethodsBetween January 2010 and August 2011, 60 patients who underwent cementless THA were randomly assigned to receive either ZA infusion or placebo (0.9% normal saline only) postoperatively. ZA was administered at 2 day and 1 year postoperatively. Periprosthetic BMD in seven Gruen zones was assessed preoperatively and at given time points for 2 years. Serum markers of bone turnover, functional scales, and adverse events were recorded.ResultsEach group contained 27 patients for the final analysis. The loss of BMD across all Gruen zones (significantly in zones 1 and 7) up to 2 years postoperatively was noted in the placebo group. BMD was significantly higher in the ZA group than in the placebo group in Gruen zones 1, 2, 6, and 7 at 1 year and in Gruen zones 1, 6, and 7 at 2 years (p < 0.05). Compared with baseline measures of BMD, the ZA group had increased BMD in zones 1, 2, 4, 5, 6, and 7 at 1 year and in zones 1, 4, 6, and 7 at 2 years (p < 0.05). Serum bone-specific alkaline phosphatase and N-telopeptide of procollagen I levels were significantly increased at 6 weeks in the placebo group and decreased after 3 months in the ZA group. A transient decrease in osteocalcin level was found at 6 months in the ZA group. Functional scales and adverse events were not different between the two groups.ConclusionsThe loss of periprosthetic BMD, especially in the proximal femur (zones 1 and 7), after cementless THA could be effectively reverted using ZA. In addition, bone turnover markers were suppressed until 2 years postoperatively following ZA administration.Trial registrationChang Gung Memorial Hospital Protocol Record 98-1150A3, Prevention of Periprosthetic Bone Loss After Total Hip Replacement by Annual Bisphosphonate Therapy, has been reviewed and will be made public on ClinicalTrials.gov. Trial registration number: NCT02838121. Registered on 19 July, 2016.

PROSTATE CANCER;

Background: Androgen deprivation therapy (ADT) with luteinizing hormonereleasing hormone agonists (LHRHa) is a major treatment modality for prostate cancer (PC),particularly advanced disease. LHRHa induced hypogonadism promotes bone loss, leading toosteoporosis and heightened fracture risk. Most previous studies on skeletal impact of LHRHaemployed bone mineral density (BMD) testing. Serum bone-specific alkaline phosphatase(BSAP), an established bone biomarker, is reflective of changes in skeletal metabolism whichprecede BMD changes. In postmenopausal women, serum BSAP has been associated withfracture risk irrespective of BMD. Setting: Charing Cross Hospital, London, United Kingdom.Methods: We assessed early changes in serum BSAP levels of patients with non-metastaticPC (n=9) undergoing LHRHa therapy. Serum testosterone and estradiol concentrations werealso measured. Samples were taken at baseline before the start of treatment and three monthsafterward. Comparisons were made with blood samples taken at similar time points for agematchedcontrols without PC (n=9). Results: No significant difference in BSAP levels wasseen between groups (p=0.242). Testosterone and estradiol levels were significantly reducedfollowing treatment (p=0.000). No correlation was observed between serum BSAP and serumtestosterone (R=0.187, p=0.276) or serum estradiol (R=0.055, p=0.75). Conclusions:Changes in serum BSAP levels may not be evident as early as 3 months following ADT withLHRHa. The study was limited by the small sample size and use of serum BSAP only whichis one of the many bone markers. A larger study using multiple bone markers is warranted todetermine early effects of LHRHa treatment on bone metabolism.

Mechanical factors and vitamin D deficiency in schoolchildren with low back pain: biochemical and cross-sectional survey analysis.

ObjectiveThis study was designed to evaluate the role of vitamin D, muscle fatigue biomarkers, and mechanical factors in the progression of low back pain (LBP) in schoolchildren.BackgroundChildren and adolescents frequently suffer from LBP with no clear clinical causes, and >71% of schoolchildren aged 12–17 years will show at least one episode of LBP.Materials and methodsA total of 250 schoolchildren aged 12–16 years were randomly enrolled in this study. For all schoolchildren height, weight, percentage of daily sun exposure and and areas of skin exposed to sun, method of carrying the bag, and bag weight and type were recorded over a typical school week. Pain scores, physical activity (PA), LBP, serum vitamin 25(OH)D level, serum bone-specific alkaline phosphatase, creatine kinase (CK), and lactate dehydrogenase (LDH) activities and calcium (Ca) concentrations were estimated using prevalidated Pain Rating Scale, modified Oswestry Low Back Pain Disability Questionnaire, short-form PA questionnaire, and colorimetric and immunoassay techniques.ResultsDuring the period of October 2013–May 2014, LBP was estimated in 52.2% of the schoolchildren. It was classified into moderate (34%) and severe (18%). Girls showed a higher LBP (36%) compared with boys (24%). In schoolchildren with moderate and severe LBP significantly higher (P=0.01) body mass index, waist, hip, and waist-to-hip ratio measurements were observed compared with normal schoolchildren. LBP significantly correlated with less sun exposure, lower PA, sedentary activity (TV/computer use), and overloaded school bags. In addition, schoolchildren with severe LBP showed lower levels of vitamin 25(OH)D and Ca and higher levels of CK, LDH, and serum bone-specific alkaline phosphatase compared with moderate and healthy schoolchildren. Stepwise regression analysis revealed that age, gender, demographic parameters, PA, vitamin D levels, Ca, CK, and LDH associated with ~56.8%–86.7% of the incidence of LBP among schoolchildren.ConclusionIn children and adolescents, LBP was shown to be linked with limited sun exposure, inadequate vitamin D diets, adiposity, lower PA, sedentary lifestyles, vitamin 25 (OH) D deficiency, and lower levels of Ca, CK, and LDH.

Serum 25-hydroxyvitamin D cutoffs for functional bone measures in postmenopausal osteoporosis.

There is no consensus on the minimal serum 25-hydroxyvitamin D [25(OH)D] concentration required to maintain bone health. The aim of this study was to investigate the relationship between 25(OH)D measured via liquid chromatography-mass spectrometry (LC-MS/MS), which is the current gold standard, and biochemical markers of bone turnover, PTH, and bone mineral densitometry (BMD). The medical records of 750 postmenopausal women newly diagnosed with osteoporosis or osteopenia at Samsung Medical Center from 2009 to 2014 were investigated. Subjects were divided into four groups according to serum 25(OH)D concentration: <10, 10-20, 20-30, and ≥30ng/mL. Serum concentrations of bone-specific alkaline phosphatase (BS-ALP), carboxy-terminal cross-linking telopeptide of type 1 collagen (CTx), intact PTH (iPTH), and BMD were compared among the four groups using analysis of covariance. Thresholds of 25(OH)D were then assessed using spline plots and locally weighted regression smoothing (LOESS) plots. 25(OH)D was negatively correlated with serum BS-ALP, CTx, and iPTH. Only femur neck and total femur BMD had significant positive relationships with 25(OH)D. Cutoff values of 11.9 and 9.7ng/mL were estimated from the spline plots of femur neck and total femur BMD, respectively. For iPTH, the LOESS plot showed a steep decrease to a serum 25(OH)D concentration of about 20ng/mL, followed by a plateau. According to this study, a serum 25(OH)D concentration of 20ng/mL, rather than 30ng/mL, was appropriate for bone health.

Investigating the Effects of Systemically Administered Strontium Ranelate on Alveolar Bone Loss Histomorphometrically and Histopathologically on Experimental Periodontitis in Rats.

The aim of this study is to investigate effects of strontium ranelate (SR) on alveolar bone loss (ABL) in rats with experimental periodontitis. Forty Wistar rats were randomly divided into five groups: 1) control (n = 8); 2) ligated (n = 8); 3) 300 mg/kg SR (SR300, n = 8); 4) 625 mg/kg SR (SR625, n = 8); and 5) 900 mg/kg SR (SR900, n = 8). To create experimental periodontitis, 4/0 silk ligatures were inserted submarginally around first molars at the right mandible. After 11 days, rats were sacrificed. ABL was calculated by measuring cemento-enamel junction and alveolar crest distance. Interleukin (IL)-1β, osteoprotegerin (OPG), and bone-specific alkaline phosphatase (BALP) serum levels were determined by enzyme-linked immunosorbent assay. Histopathologic analysis was used to evaluate inflammatory cell infiltration, numbers of osteoblasts and osteoclasts, and receptor activator of nuclear factor-kappa B ligand (RANKL) activity. ABL was significantly lower in SR900 group than in the ligated group (P <0.05). Osteoclast numbers in ligated group were significantly higher than in the control, SR300, and SR900 groups (P <0.05). In ligated, SR625, and SR900 groups, significantly higher osteoblast numbers were detected than in control group (P <0.05). Osteoblast numbers in SR625 group were significantly higher than in the SR300 group (P <0.05). RANKL activities in SR900 and control groups were close to each other (P >0.05). Serum IL-1β, OPG, and BALP levels revealed no significant difference (P >0.05). It can be concluded that SR can reduce RANKL activity and osteoclast numbers, as well as ABL.

Effects of Yishengukang decoction on expression of bone-specific alkaline phosphatase, carboxyterminal propeptide of type I procollagen, and carboxyterminal cross-linked telepeptide of type I collagen in malignant tumor patients with bone metastasis

OBJECTIVETo investigate the effect of Yishengukang decoction on the expression of the metabolic bone markers, bone-specific alkaline phosphatase (BAP), carboxyterminal propeptide of type I procollagen (PICP), and carboxyterminal cross-linked telepeptide of type I collagen (ICTP), in cancer patients with bone metastasis. METHODSPatients (n = 180) were divided into three groups: (a) bone metastasis patients treated with Yishengukang and pamidronate disodium injection (treatment group, n = 60); (b) bone metastasis patients treated with pamidronate disodium injection alone (control group, n = 60); (c) cancer patients without metastatic bone lesion (non-bone metastasis group, n = 60). Serum levels of the metabolic markers BAP, PICP, and ICTP were detected by enzyme-linked immunosorbent assay pre- and post-therapy. RESULTSA significant decrease in serum BAP level was observed in the treatment group compared with the control group. However there were no significant differences in serum levels of PICP and ICTP before or after treatment compared with the control group. CONCLUSIONYishengukang decoction combined with pamidronate disodium injection reduced serum BAP level to a greater extent that pamidronate disodium injection alone. Furthermore, the combined therapy was more beneficial in regulating imbalanced bone metabolism after bone metastasis, and may represent the molecular mechanism underpinning the effects of Yishengukang decoction.

Effects of glucocorticoid-induced osteoporosis on bone tissue of rats with experimental periodontitis

ObjectiveTo evaluate the effects of osteoporosis induced by glucocorticoid (GIOP) on bone tissue of rats with experimental periodontitis (EP). Design48 male Wistar rats divided into groups: Naïve, EP, GIOP and GIOP+EP. Rats of GIOP and GIOP+EP groups received 7mg/kg of dexamethasone intramuscularly once a week for 5 weeks. Following, EP and GIOP+EP groups were subjected to ligature-induced periodontitis. Naïve group experienced no manipulation. After 11 days, the animals were euthanized and left maxillae collected for macroscopic, radiographic, micro-tomographic and microscopic analysis of alveolar bone loss (ABL). Blood samples were collected for determination of bone-specific alkaline phosphatase (BALP) levels and the right femurs were removed for radiographic and biomechanical analysis. ResultsEP caused ABL and reduced BALP levels (p<0,05), but it did not change the architecture or biomechanics of femur, compared to Naïve. GIOP did not cause ABL, but it significantly decreased alveolar bone mineral density (ABMD), bone percentage and trabecular thickness (Tb.Th) and increased alveolar bone porosity (p<0.05) and significantly reduced BALP serum levels, as well as radiographic density and Young’s module of femur, compared to Naïve. There was a greater ABL in group GIOP+EP when compared to EP (p<0.05). GIOP+EP caused a greater decrease on ABMD, Tb.Th, bone percentage and increased bone porosity (p<0.05) and also presented a significant reduction in BALP levels (p<0.05), in radiographic density and in Young’s module of femur compared to EP (p<0.05). ConclusionsGIOP can potentiate the destructive effects of EP on alveolar bone and alter the systemic bone loss, by promoting bone resorption and reducing osteoblast activity.

Bone health assessment by quantitative ultrasound and dual-energy x-ray absorptiometry in postmenopausal women with breast cancer receiving aromatase inhibitors.

Phalangeal quantitative ultrasound (QUS) measurements provide surrogate information on bone quality. The aim of the present study was to assess bone status by phalangeal QUS and by dual-energy x-ray absorptiometry (DXA), and to evaluate bone turnover in breast cancer (BC) women receiving aromatase inhibitors (AIs). Sixty postmenopausal BC women and 42 matched controls were recruited (mean age 61.64 ± 8.33 y). Amplitude-dependent speed of sound (AD-SoS), bone transmission time (BTT), Ultrasound Bone Profile Index, as QUS parameters, L1-L4 and femoral neck BMD by DXA were assessed at baseline and after 18 months; serum bone-specific alkaline phosphatase (BSAP) and C-telopeptide of type 1 collagen were measured at baseline, 9 and 18 months. FRAX (without BMD) derived 10-years probability of major fractures and hip fractures were significantly associated with AD-SoS (r = -0.381, P = < 0.001 and r = -0.370, P < 0.001, respectively), Ultrasound Bone Profile Index (r = -0.434, P ≤ 0.001 and r = -0.409, P = < 0.001, respectively), BTT (r = -0.309, P = 0.002 and r = -0.340, P = 0.001, respectively). The median percent changes of AD-SoS (-3.71 [-5.38 to 0.11] vs -0.7 [-4.15 to 0.83], P = 0.02 respectively), BTT (-8.4 [-14.91 to -3.53] vs -1 [-5.72 to 3.75], P < 0.001 respectively) were significantly different between AIs users and controls. The same trend was observed for DXA measurements. BSAP and C-telopeptide of type 1 collagen significantly changed in AIs users. AD-SoS was associated with change of BMD at lumbar spine (β, 0.16; SE, 0.08; P = 0.04) and change of BSAP (β, -0.04; SE, 0.02; P = 0.04). Phalangeal QUS appeared a useful tool to evaluate bone quality in BC women on AIs.

Bone mass and bone turnover in premenopausal women with fibromyalgia syndrome

In this study, we aimed to compare osteoporosis (OP)-related bone mineral density, and bone turnover (markers of formation, and resorption) between patients with Fibromyalgia Syndrome (FMS) and degenerative disc disease, and to determine the relationship of these parameters with clinical, functional and emotional evaluation outcomes in FMS. Fifty premenopausal women with FMS and 50 premenopausal female control patients with degenerative disc disease were enrolled. The patient and physician’s global assessment of disease were assessed on a visual analog scale (VAS). Disease severity was determined with the Fibromyalgia Impact Questionnaire (FIQ). For the evaluation of fatigue The Modified Fatigue Impact Scale (MFIS) and Fatigue Severity Scale (FSS) were used. The quality of life of all patients was evaluated using Nottingham Health Profile (NHP), Oswestry Disability Index (ODI), and QUALEFFO-41. The emotional state of all patients with chronic pain was evaluated with Hospital Anxiety and Depression Scale (HADS). Bone turnover markers [serum bone-specific alkaline phosphatase (bALP) and serum osteocalcin as markers of bone formation, serum â-isomerized Carboxy-terminal telopeptide of collagen type I (â-CTX) and urine hydroxyproline (OH-Pro) as markers of bone resorption], serum parathyroid hormone (PTH) and 25-hydroxyvitamin D [25(OH)D] levels, lumbar spine and left proximal femur bone mineral density (BMD) and T scores were measured in both groups. The FIQ, MFIS, FSS, NHP, ODI, QUALEFFO-41, HADS-A and HADS-D scores were statistically significantly higher in the FMS group relative to the patient control group. A significant difference between FMS and patient control group as for bone formation (bALP and osteocalcin) and resorption (â-CTX ve OH-Pro) markers was not detected. In the FMS group lumbar spine and left proximal femur BMD and T score values were significantly lower when compared with the patient control group. In the FMS group significant correlations were found between serum 25(OH)D and â-CTX values and VAS scores evaluated by the patient and physician, SS scale, FIQ, MFIS, ODI, QUALEFFO-41 and NHP scores. In conclusion many factors including depression and anxiety attacks, the presence of widespread pain and a decline in physical activity level and quality of life in FMS patients make them more prone to osteoporosis. In patients with FMS, osteoporosis is a major cause of morbidity and should not be neglected.

Effect of soy isoflavones supplement on climacteric symptoms, bone biomarkers, and quality of life in Korean postmenopausal women: a randomized clinical trial.

BACKGROUND/OBJECTIVESSoy isoflavones are expected to improve menopausal symptoms and osteoporosis in women. However, their efficacy is still inconclusive, and there was limited data for postmenopausal women in South Korea. We examined the effects of soy isoflavones on climacteric symptoms, bone biomarkers, and quality of life in Korean postmenopausal women.SUBJECTS/METHODSA randomized, double-blind study design was used. Eighty-seven participants who had undergone natural menopause were randomly administered either 70 mg/day isoflavones (n = 43) or placebo (n = 41) for 12 weeks. We assessed the Kupperman index for climacteric symptoms and the menopause-specific quality of life (MENQOL) questionnaire for quality of the life. Biomarkers of bone metabolism were also measured in serum bone-specific alkaline phosphatase (BALP), osteocalcin (OC), N- and C-terminal cross-linking telopeptides of type I collagen (NTx, CTx), and urine-deoxypyridinolin (u-DPD).RESULTSScores of the Kupperman index were decreased in both the isoflavones group (−7.0 ± 15.8, P = 0.0074) and placebo group (−6.3 ± 14.6, P = 0.0064) during the intervention, but no significant difference was noted between the groups. Regarding the bone formation markers, the level of serum BALP increased by 6.3 ± 4.1% (P = 0.004) and OC increased by 9.3 ± 6.2% (P < 0.001), meanwhile those of the placebo were not changed. For the bone resorption markers, NTx, CTx, and u-DPD were not significantly different in either group. MENQOL was significant decreased in the isoflavone group (−0.6 ± 0.5) and placebo group (−0.6 ± 0.4), with a significant difference between groups (P = 0.0228).CONCLUSIONSOur study suggests that 70 mg isoflavones supplement has beneficial effects on bone formation markers; however, it showed no benefit compared to the placebo on climacteric symptoms or quality of life.

Effects of Denosumab on Bone Metabolic Markers and Bone Mineral Density in Patients Treated with Glucocorticoids.

Objective We performed a prospective study to determine the efficacy and safety of denosumab on bone metabolic indices and bone mineral density (BMD) in 29 patients receiving long-term glucocorticoids (GCs) who had clinical risk factors for fracture. Methods Among these patients, 16 had systemic lupus erythematosus (SLE), 6 RA, 4 other autoimmune diseases, and 3 renal diseases. All patients received donosumab 60 mg at baseline and 6 months. Serum N-terminal cross-linked telopeptide of type I collagen (NTX) and bone-specific alkaline phosphatase (BAP) levels were measured as bone metabolic indices. BMD at the lumbar spine (LSBMD) and femoral neck (FNBMD) were measured using dual energy X-ray absorptiometry and expressed as a percentage of the young adult mean (%YAM). Results Denosumab therapy significantly reduced serum NTX and BAP levels from baseline after 12 months (from 19.2 to 13.9 nmol BCE/L; from 11.9 to 9.2 U/L, respectively). In 18 patients treated with bisphosphonates before the start of denosumab therapy, the improvements in the LSBMD and FNBMD values were 1.5%YAM/year and 1.1%YAM/year, respectively. The LSBMD and FNBMD values were both significantly higher 12 months after denosumab therapy (3.5%YAM/year and 3.0%YAM/year, respectively). The LSBMD gain was significantly higher after denosumab therapy than during bisphosphonate therapy. No fractures were observed in any patients during denosumab therapy. Conlusion Denosumab is effective and safe in preventing bone resorption and BMD loss in patients treated with long-term GCs for inflammatory diseases. This is the first study showing a significant increase in not only LSBMD but also FNBMD in GC-induced osteoporosis after denosumab therapy.

Safety and efficacy of tocotrienol supplementation for bone health in postmenopausal women: protocol for a dose–response double-blinded placebo-controlled randomised trial

IntroductionOsteoporosis is a major health concern in postmenopausal women, and oxidative stress contributes to the development of bone loss. Cellular studies and ovariectomised rat model mimicking bone loss in postmenopausal...

Novel therapeutic intervention for osteoporosis prepared with strontium hydroxyapatite and zoledronic acid: In vitro and pharmacodynamic evaluation

Osteoporosis therapeutics has been monopolized mainly by bisphosphonates, which are potent anti-osteoporotic drugs, while they do not promote bone formation or replenish the already resorbed bone. Although strontium substituted hydroxyapatite (SrHA) has been proclaimed to improve bone properties in an osteoporotic animal model, there is no published data on direct delivery of SrHA nanoparticles by bisphosphonate-like zoledronic acid (ZOL) to the bone. Therefore, this study was designed to investigate the potential of using SrHA/ZOL nanoparticle-based drug formulation in an ovariectomized rat model of postmenopausal osteoporosis. SrHA and SrHA/ZOL nanoparticles were prepared and characterized by field-emission scanning electron microscopy (FESEM), X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR). Twelve weeks after ovariectomy, rats were treated with either single intravenous dose of SrHA/ZOL (100, 50 or 25μg/kg); ZOL (100μg/kg); or SrHA (100μg/kg). Saline-treated OVX and SHAM-OVX groups served as controls. The energy-dispersive X-ray (EDX) microanalysis of bone specimen obtained from SrHA/ZOL groups yielded range between 64.3±6.7 to 66.9±6.8 of calcium weight (wt) % and 1.64±0.6 to 1.74±0.8 of calcium/phosphorus (Ca/P) ratio which was significantly higher when compared with 39.7±9.3 calcium and 1.30±0.2 Ca/P ratio for OVX group. Moreover, the strontium wt% in SrHA/ZOL group (between 3.1±0.5 and 6.8±0.4) was significantly higher than SrHA group (1.8±0.9). These results confirmed targeted delivery of SrHA nanoparticles by ZOL to the bone. Therapy with SrHA/ZOL showed significant improvements in trabecular bone microarchitecture and mechanical strength as compared to ZOL or SrHA (p<0.05). Moreover, treatment with SrHA/ZOL significantly precluded an increase in serum bone-specific alkaline phosphatase and tartrate-resistant acid phosphatase than either ZOL or SrHA (p<0.05). These results strongly implicate that SrHA/ZOL nanoparticle-based drug formulation showed better efficacy at a much lower dose of ZOL. SrHA/ZOL drug formulation has a therapeutic advantage over ZOL or SrHA monotherapy for experimental osteoporosis.

Serum N-terminal telopeptide of type I collagen as an early marker of fracture nonunion in rabbits.

The aim of the present study was to establish an experimental animal model of fracture nonunion, and to investigate the changes in serum biomarker concentrations in fracture nonunion. A total of 20 purebred New Zealand rabbits were divided into two group: A bone defect group and a bone fracture group. In the bone defect group, a 15-mm section of bone (including the periosteum) was removed from the mid-radius, and the medullary cavities were closed with bone wax. In the bone fracture group, the mid-radius was fractured. X-rays were taken and blood samples were collected preoperatively and at 2, 3, 4, 5, 6, 7, 8, 10 and 12 weeks after the surgical procedure. The serum concentrations of osteocalcin (OC) and bone-specific alkaline phosphatase (BSAP) served as markers of bone formation, and those of C-terminal telopeptide of type I collagen (CTX), N-terminal telopeptide of type I collagen (NTX) and tartrate-resistant acid phosphatase 5b (TRACP 5b) served as markers of bone resorption. The concentration levels of the markers were measured using a biotin double-antibody sandwich enzyme-linked immunosorbent assay. In the bone defect group, bone callus was observed on X-ray at 2 weeks in three rabbits and the bone calluses stabilized at 5 weeks; however, none of the bones had healed at 8 weeks. In the bone fracture group, the fracture line was distorted at 2 weeks and bone calluses formed at 6–8 weeks. In the bone defect group, the serum BSAP and TRACP 5b concentrations increased following the surgical procedure, peaked at 4 weeks, began to decrease at 5 weeks and stabilized after 6 weeks. The serum OC concentrations did not change significantly following the surgical procedure. The serum CTX concentrations fluctuated during the first 4 weeks, peaked at 5 weeks, then decreased and stabilized after 6 weeks. The serum NTX concentrations fluctuated during the first 4 weeks, were significantly lower at 5 weeks compared with the other time points and stabilized after 6 weeks. These results suggested that a bone nonunion model can be established in New Zealand rabbits by resecting a 15-mm section of bone from the mid-radius prior to bone wax blocking. Measurement of the serum BSAP, CTX, NTX, and TRACP 5b concentrations may be useful for the early detection of bone nonunion. The serum NTX concentrations changed significantly in rabbits with bone nonunion. Further studies are required in order to determine the feasibility of using serum NTX concentrations for the early diagnosis of bone nonunion.