Changes In Markers Of Bone Metabolism Research Articles

Comparison of the Efficacy of Zoledronate Acid or Denosumab After Switching from Romosozumab in Japanese Postmenopausal Patients.

We aimed to compare the efficacy of switching from romosozumab (RMAb) to denosumab (DMAb) or zoledronic acid (Zol) with respect to changes in bone mineral density (BMD) and bone metabolism. We also aimed to determine predictors of changes in BMD among patients who received sequential therapy from RMAb. One hundred patients who received RMAb therapy were recruited for this study. A total 49 patients received bisphosphonate (BP) pre-treatment and 51 received active vitamin D3 analog pre-treatment or no treatment. Forty-two patients were switched to Zol (BP-RMAb-Zol; 20 and RMAb-Zol; 22), and 58 patients were switched to DMAb (BP-RMAb-DMAb; 29 and RMAb-DMAb; 29). Longitudinal changes in bone metabolic markers (P1NP and TRACP-5b) and BMD were also evaluated. In the BP-RMAb-Zol group, TRACP-5b increased after administration of Zol, and the mean BMD of the lumbar spine (LS) was significantly lower than those in the BP-RMAb-DMAb, RMAb-Zol and RMAb-DMAb groups at 24months. The % changes in BMD of the LS after 24months were associated with TRACP-5b values at baseline and at 12months in patients who received Zol therapy, and with TRACP-5b value at baseline in patients who received DMAb therapy. The DMAb follow-on regimen could be considered more effective than Zol as a sequential agent for the enhancement of BMD after RMAb in patients with BP pretreatment. TRACP-5b, especially the baseline value, may predict the efficacy of sequential therapy from RMAb, as well as previous treatments.

Changes Of Bone Metabolism Markers In Japanese Male Long Distance Runners During In-season

Stress fracture is one of the most common overuse injuries in runners and there are many risk factors that predispose to this injury. Previous studies have focused on bone metabolism and the correlation between stress fractures and bone metabolism has been reported. However, most studies are on female athletes, and little is known on male athletes. Moreover, long-term bone metabolic process in athletes is unknown. PURPOSE: To investigate changes bone metabolism markers in male long distance runners during in-season METHODS: Twenty-five male long distance runners participated in this study, and total of 11 athletes were qualified for analysis (24 ± 4.3 yrs, 170.4 ± 5.0 cm, 55.9 ± 3.7 kg) after excluding those who were injured and/or were not able to run more than 200 km per month. Blood samples were collected from 9 am to 11 am during pre-season (PRs), post-track season (PTs), and road-race season(RRs). Athletes were instructed to refrain from training prior to blood collection. To assess bone metabolism bone-specific alkaline phosphatase(BAP) and tartrate-resistant acid phosphatase-5b(TRACP-5b) were measured. In addition, athletes reported their monthly training volume of one month prior the first measurement. Changes of bone metabolic markers were assessed by one-way ANOVA with repeated measures and correlations between training volume and both markers were made using Spearman’s rank correlation coefficient. RESULTS: BAP in PTs (14.98 ± 3.11 vs. 16.62 ± 3.76 p = 0.004) and RRs (14.85 ± 3.68 vs. 16.62 ± 3.76 p = 0.004) were significantly lower than that of PRs. There were no statistically significant changes in TRACP-5b. Moreover, there were not any correlations between monthly training volume and both bone metabolism markers. CONCLUSIONS: We found that BAP lower than PRs from the latter half of track season to the road race season.

Strontium-89 plus zoledronic acid versus zoledronic acid for patients with painful bone metastatic breast cancer

β-ray strontium-89 (Sr-89) intra-irradiation therapy has been approved and clinically used to reduce bone metastasis pain not alleviated by bone-modifying agents, external radiation, and analgesic agents. We examined the efficacy of zoledronic acid (ZOL) and Sr-89 combination therapy compared with ZOL alone in breast cancer patients with bone metastases. A randomized controlled trial was conducted on breast cancer patients with bone metastasis to compare the efficacy between ZOL monotherapy and ZOL plus Sr-89 combination therapy. The primary endpoints were changes in urinary NTX levels at 13weeks and brief pain inventory scores. The secondary endpoints were analgesic drug usages, response rates, changes in bone metabolism markers, quality of life, and adverse event rates. Thirty of the planned 60 cases were randomly assigned to ZOL alone or ZOL + Sr-89. There were no significant differences in the changes in urinary NTX levels between the 2 groups (P = 0.365). There was no consistent difference in the pain score changes between the 2 groups. Sr-89 addition to ZOL slightly reduced the white blood cell and platelet counts. However, all adverse events were Grade 1. Safety and analgesic drug dose reduction were more evident in ZOL + Sr-89. This trial showed the lack of benefits from Sr-89 addition to ZOL for breast cancer patients with painful bone metastases. However, safety and analgesic drug dose reduction were more evident in ZOL + Sr-89, indicating its potential for pain control. Sr-89 therapy is safe, thus more effective radiopharmaceuticals are anticipated.

Effects of alendronate sodium combined with InterTan on osteoporotic femoral intertrochanteric fractures and fracture recurrence.

BACKGROUNDOsteoporosis is a global disease affecting 6.6% of the total population. Osteoporosis complications include fractures, increased bone fragility, and reduced bone strength. The most commonly affected parts are the vertebral body, hip, and wrist. AIMTo examine the effect of alendronate sodium combined with InterTan for osteoporotic femoral intertrochanteric fractures on bone and fracture recurrenceMETHODSIn total, 126 cases of osteoporotic femoral intertrochanteric fractures were selected and divided into two groups according to the 1:1 principle by the simple random method. They were admitted to the Department of Orthopedics, First Affiliated Hospital of Xingtai Medical College, from January 2018 to September 2020. The control group was treated with InterTan fixation combined with placebo, and the observation group with alendronate sodium based on InterTan fixation. Operation-related indicators, complications, and recurrent fractures were compared between the groups. Changes in bone metabolism markers, t value for hip bone mineral density, and Harris Hip Score were observed.RESULTSOperation time, intraoperative blood loss, postoperative ambulation time, and complications were compared between the groups, and no significant difference was found. The fracture healing time was significantly shorter in the observation group than in the control group. β-Collagen-specific sequence (β-CTX) and total aminoterminal propeptide of type I procollagen (T-PINP) in the control group at 3 mo after operation were compared with those before operation, and the difference was not significant. Six months after the operation, the β-CTX level decreased and T-PINP level increased. β-CTX level at 3 and 6 mo in the observation group after operation was lower, and T-PINP level was higher, than that before operation. Compared with the control group, T-PINP level of the observation group was significantly higher and β-CTX level was significantly lower at 3 and 6 mo after operation. The t value of hip bone mineral density was compared in the control group before and 1 mo after operation, and significant difference was not found. Compared with the control group, the t value of hip bone mineral density in the observation group was significantly higher at 1, 3, 6, and 12 mo after operation. Compared with the control group, the Harris score of the observation group was significantly higher at 1, 3, 6, and 12 mo after operation. The recurrence rate of fractures in the observation group within 12 mo was 0.00%, which was significantly lower than 6.35% in the control group. CONCLUSIONAlendronate sodium combined with InterTan in the treatment of osteoporotic femoral intertrochanteric fractures can increase bone mineral density, improve hip joint function, promote fracture healing, and reduce fracture recurrence.

Clinical Implications of Bone Metabolic Markers in Patients with Type 2 Diabetes Mellitus

This paper compared the changes of bone metabolic markers (BTM) in patients with Type 2 Diabetes Mellitus (T2DM) with or without diabetic kidney disease (DKD). 204 T2DM patients were divided into 4 groups, such that group 1 had no albuminuria, group 2 had microalbuminuria, group 3 with macroalbuminuria, and group 4 with DKD according to urine albumin and albumin to creatinine ratio (ACR) and levels of serum creatinine (SCR). The ACR, SCR, uric acid (UA), osteocalcin (OC), procollagen type I N-terminal propeptide (PINP), C-terminal telopeptide of type I collagen (CTX) and bone mineral density of the lumbar vertebrae 1-4 (BMDLV) in DKD were considerably higher than those who were non-DKD (P<0.05). When there is no DKD in diabetes, ACR detection is the most sensitive and specific. When it comes to DKD, the SCR is the most sensitive, and PINP specificity is greater than CTX, but the sensitivity is lower. DKD is a major contributor to osteoporosis risk.

Development of a Chemiluminescence Assay for Total N-Terminal Propeptide of Type I Collagen and Its Evaluation in Lung Transplantation.

Serum P1NP, one of the important biomarkers for bone turnover, is commonly used for the prediction of bone fracture and the prognosis of osteoporosis after therapy. We developed a P1NP chemiluminescence assay and evaluated changes in bone metabolism markers in lung transplant patients. The screened 2 P1NP antibodies with constructed antigens and α-1 chain antigens expressed by the Corynebacterium glutamate expression system were applied into assay development. The assay performance was evaluated to examine the reliability. A normal Q-Q plot was used to establish male reference interval. Changes of bone metabolism markers before and after lung transplantation in 19 patients were evaluated. The linear factor R of P1NP reagent was greater than 0.99. The limit of detection was 3.32 ng/ml. The precision of the three batches of P1NP reagents was lower than 8%. Method comparison with Roche P1NP reagent showed that the correlation coefficient R2 was 0.91. In the monitoring of bone mass in a short time, bone metabolism markers can better indicate the change of bone mass, while the traditional bone mineral density detection is lagging behind the bone metabolism markers. P1NP and β-CrossLap to bone mass change in patients after lung transplantation, and P1NP and β-CrossLap are very good clinical markers for bone mass monitoring.

Longitudinal Changes in Serum Markers of Bone Metabolism and Bone Material Strength in Premenopausal Women with Distal Radial Fracture.

Markers of bone metabolism (MBM) play an important role in fracture evaluation, and changes have been associated with increased fracture risk. The purpose of the present study was to describe changes in MBM in premenopausal women with distal radial fractures. Premenopausal women with distal radial fractures (n = 34) and without fractures (controls) (n = 39) were recruited. Serum MBM in patients with distal radial fractures were obtained at the time of the initial presentation, 6 weeks, and 3, 6, and 12 months. MBM included 25(OH) vitamin D, PTH, osteocalcin, P1NP, BSAP, CTX, sclerostin, DKK1, periostin, and TRAP5b. Areal bone mineral density (aBMD) was assessed with dual x-ray absorptiometry, and the bone material strength index (BMSi) was assessed with microindentation. Most MBM reached peak levels at 6 weeks after the injury, including osteocalcin (+17.7%), sclerostin (+23.5%), and DKK1 (12.6%). Sclerostin was lower (-27.4%) and DKK1 was higher (+22.2%) at 1 year after the fracture. CTX declined below baseline levels at 6 and 12 months, whereas TRAP5b, BSAP, and periostin did not significantly change. At 12 months, sclerostin was lower (p = 0.003) and DKK1 was higher (p = 0.03) in the distal radial fracture group than in the control group. Greater fracture severity was associated with greater increases in P1NP and BSAP. aBMD and BMSi were not associated with fracture. Distal radial fractures caused increases in several MBM, which typically peaked at 6 weeks after injury and gradually decreased over 6 months. Sclerostin and DKK1 remained below and above baseline at 1 year, respectively. Increasing fracture severity resulted in larger changes in MBM. aBMD and BMSi did not discriminate between patients with distal radial fractures and controls. Continued efforts to identify markers of skeletal fragility in young women are warranted to mitigate future fracture risk. Prognostic Level II. See Instructions for Authors for a complete description of levels of evidence.

Utility of monthly minodronate for osteoporosis after gastrectomy: Prospective multicenter randomized controlled trials.

AimOsteoporosis in patients after gastrectomy is increasing with the aging of gastric cancer patients. Bisphosphonates are effective treatments for osteoporosis; however, their safety or efficacy in postgastrectomy patients has not been established. The purpose of this multicenter prospective intervention study was to investigate the impact of monthly minodronate on osteoporosis after gastrectomy.MethodsOf the 261 enrolled gastric cancer patients, 164 patients were diagnosed with osteoporosis based on criteria of the Japan Society of Osteoporosis. They were randomly assigned 1:1 to groups treated with active vitamin D (VD group) or monthly minodronate (MIN group). The primary endpoint was changes in lumbar bone mineral density (L‐BMD) 12 mo after the start of administration. The secondary endpoints were changes in bone metabolism markers, adverse events (AEs), or treatment completion rates.ResultsThere was no significant difference in patient background between the VD (n = 82) and MIN (n = 82) groups. In the MIN group, the increase in L‐BMD was significantly higher than that in the VD group (4.52% vs 1.72%, P = .001), with a significant reduction in bone metabolism markers; blood NTX (−25.6% vs −1.6%, P < .01) and serum bone‐specific alkaline phosphatase (−34.3% vs −20.1%, P < .01). AEs were observed in 26.8% and 9.3% of the patients and treatment completion rates were 77.5% and 89.3% in the MIN and VD groups, respectively. Serious AEs were not observed in either group.ConclusionThis study demonstrated the safety and efficacy of monthly minodronate, suggesting that this treatment may be useful for osteoporosis after gastrectomy (UMIN000015517).

Effects after starting or switching from bisphosphonate to romosozumab or denosumab in Japanese postmenopausal patients.

PurposeWe aimed to investigate the longitudinal changes in bone metabolic markers and bone mineral density (BMD) after starting or switching from bisphosphonate (BP) to romosozumab (ROMO) or denosumab (DENO) therapies over 12 months and to determine predictors that establish associations with changes in BMD among the patients received the ROMO therapy.MethodsPostmenopausal osteoporosis patients with a high risk of fracture—154 in total—were recruited; their therapies were switched to ROMO or DENO from BP/naïve or vitamin D (ND) (ND-ROMO: 43, BP-ROMO: 38, ND-DENO: 38, and BP-DENO: 35). Longitudinal changes in bone metabolic markers and BMD were evaluated.ResultsROMO groups showed significant increases in BMD of the lumbar spine at 6 and 12 months and femoral neck at 12 months compared to the DENO groups. Although BP-ROMO showed significant increase in the lumbar spine BMD compared to BP-DENO, there were no significant differences in femoral neck and total hip BMDs between BP-ROMO and BP-DENO. Among the ROMO groups, % changes of BMD from baseline to 12 months were associated with bone metabolic markers at baseline and changes in TRACP-5b from baseline to 3 months.ConclusionsROMO continuously increased BMD for 12 months and performed better than DENO. On the other hand, effects of ROMO switched from BP on BMD of femoral neck and total hip were almost same with DENO. Bone metabolic markers at baseline and changes in TRACP-5b from baseline to 3 months may predict the efficacy of ROMO after 12 months of administration.

Short-term efficacy and safety of zoledronate acid or denosumab in Japanese patients with postmenopausal osteoporosis

IntroductionWe aimed to compare the efficacy after switching from either bisphosphonates (BPs) or non-BPs (NBPs) to combination therapies of denosumab (DMAb) or zoledronic acid (Zol) with eldecalcitol (ELD) in bone mineral density (BMD) and bone metabolism and investigate the prognostic and risk factors of side effects of this therapy.Materials and methodsOne-hundred forty-eight patients with postmenopausal osteoporosis were recruited; their therapy was switched from BPs or NBPs to Zol or DMAb plus ELD (BP-Zol: 43, NBP-Zol: 32, BP-DMAb: 35, and NBP-DMAb: 38). Longitudinal changes in bone metabolic markers (P1NP and TRACP-5b) and BMD were evaluated.ResultsIn the BP-Zol group, P1NP did not change after 6 months and increased by 38.9% after 12 months. TRACP-5b decreased 15.8% after 6 months, but came back to baseline values 12 months after administration. In the rest of the groups, the bone metabolic markers remained suppressed after 6 and 12 months. Compared with baseline, all groups showed increase in BMD after 6 and 12 months. Bone metabolic markers at baseline were correlated with %change in lumbar spine BMD from baseline to 12 months. P1NP and 25-hydroxy vitamin D levels at baseline were identified as potential predictors of development of acute-phase reactions.ConclusionsThe combination therapy of Zol or DMAb and ELD may increase BMD at 12 months after the first administration in Japanese patients with postmenopausal osteoporosis, regardless of BPs pretreatment. Bone metabolic markers at baseline may be useful predictors for reaction to the therapy and side effects caused by these combination therapies in postmenopausal osteoporosis.

Time-Course Changes in Bone Metabolism Markers and Density in Patients with Osteoporosis Treated with Romosozumab: A Multicenter Retrospective Study.

PurposeIn this multicenter retrospective observational study, we examined the early effects of romosozumab in patients with severe osteoporosis in terms of time-course changes in bone metabolism marker, improvement in bone density, and adverse effects.Materials and MethodsPatients with severe osteoporosis were included. We investigated the progress of TRACP 5b and P1NP before and 1–2 months after the administration of romosozumab. We also investigated the bone density of lumbar spine, femoral neck, and the entire femur, measured by the DXA method, before and 5–7 months after the administration of romosozumab.ResultsA total of 70 patients (7 males and 63 females, age 75.0±3.6 years) participated in this study. Significant improvements in TRACP 5b and P1NP levels were observed before and 1–2 months after romosozumab administration. The average bone density of lumbar spine, femoral neck, and the entire femur were measured before and 5–7 months after romosozumab administration; and a significant increase only observed in the lumbar spine.ConclusionConsistent with the findings of previous clinical studies, romosozumab has both bone formation-enhancing and bone resorption effects (dual effect). In addition, romosozumab also demonstrated improvement in bone density from the early phase after the administration, though the result was only seen in the lumbar spine.

The effect of denosumab administration on bone metabolism for treatment of spinal metastasis

BackgroundWe investigated changes in bone metabolism markers over time for evaluating the effect of denosumab following administration to patients with spinal metastasis. MethodsSubjects of this study were 28 patients treated at the Department of Orthopedic Surgery at Aichi Medical University. ResultsAt 6 months after denosumab intervention, measured TRAP-5b values were significantly lower compared to pre-intervention values in both the osteosclerotic lesion and osteolytic lesion groups. ConclusionsThis change in bone metabolism marker values over time is one of the methods for evaluating the effect of treatment on bone tissue in cases of spinal metastasis.

SAT-521 Changes in Multiple Bone Metabolism Markers after Adrenalectomy in Patients with Aldosterone Producing Adenoma

<Background > In primary aldosteronism (PA), it is reported that secondary hyperparathyroidism (SHPT) is caused by increased urinary Ca excretion due to excessive aldosterone, which may decrease bone mineral density and increase fracture risk. However, there have been few reports that evaluated changes in bone metabolism markers in detail before and after the treatment for PA. In this retrospective study, we evaluated changes in multiple bone metabolism markers before and after adrenalectomy. <Methods> We analyzed 16 patients who underwent adrenalectomy for unilateral aldosterone-producing adenoma (APA) in our hospital from April 2009 to November 2017 and compared various bone metabolism markers before and after surgery. All patients were diagnosed with unilateral hyperaldosteronism by segmental adrenal venous sampling. Patients with bilateral hyperaldosteronism and bone disease were excluded. We compared changes in levels of serum Ca, 24-hour urinary Ca excretion (u-Ca), intact parathyroid hormone (iPTH), tartrate-resistant acid phosphatase 5b (TRACP-b5), bone-specific alkaline phosphatase (BAP), and undercarboxylated osteocalcin (ucOC) before and one year after surgery. <Results> Sixteen patients consisted of 8 males and 8 females (Mean age =49.6 years old, BMI =23.7 kg/m2, hypertension duration =10.9 years, blood pressure =135/84 mmHg, eGFR =86.6 mL/min/1.73 m2). After surgery, aldosterone hypersecretion improved markedly (plasma aldosterone (PAC); 278.4 ± 167.5 to 96.9 ± 47.1 pg/mL, urinary aldosterone; 28.6 ± 22.7 to 5.6 ± 3.9 μg/day). Significant increase in serum Ca (8.74 ± 0.24 to 9.31 ± 0.80 mg/dL, P < 0.001) and decreases in u-Ca (0.23 ± 0.10 to 0.09 ± 0.07 g/day, P = 0.002) and iPTH (86.7 ± 40.8 to 54.4 ±16.3 pg/mL, P < 0.001) were observed. In addition, significant decreases in TRACP-b5 (373.0 ± 180.1 to 211.9 ± 101.2 mU/dL, P < 0.001), BAP (16.6 ± 7.06 to 10.8 ± 3.73 μg/L, P < 0.001), and ucOC (7.56 ± 5.0 to 4.04 ± 2.3 ng/mL, P = 0.004) levels were observed. The change in iPTH had significant positive correlation with the change in PAC (r = 0.55, P = 0.026), while it had no correlation with the change in u-Ca. <Conclusion> The correction of hyperaldosteronism by adrenalectomy decreased urinary Ca excretion, iPTH level, and bone tune over. In addition, our results suggest that the increase in iPTH was caused by hyperaldosteronism, independent from the excess in urinary calcium excretion.

Potential association with early changes in serum calcium level after starting or switching to denosumab combined with eldecalcitol.

The aims of this study are to investigate changes in serum calcium (Ca) level after switching from either non-therapy, bisphosphonate, selective estrogen receptor modulators (SERM) or teriparatide treatments to a combination therapy of denosumab (DMAb), and eldecalcitol, and the association between early changes in serum calcium and changes in bone metabolic markers and bone mineral density (BMD). 129 patients with postmenopausal osteoporosis (32 non-pretreatment, 50 bisphosphonates, 18 SERM, and 29 teriparatide) were recruited and switched to DMAb plus eldecalcitol. Serum calcium levels, bone metabolism markers, and BMD measurements of the lumbar spine and femoral neck were evaluated. All groups showed an increase in BMD 6months and 1year after DMAb administration compared to baseline via suppression of bone metabolism markers. The TPD group showed a significant decrease in serum calcium level 1week after the first injection of DMAb and eldecalcitol compared to baseline and the bisphosphonate group. Changes in serum calcium level from baseline to 1week after the first injection of DMAb trended to correlate with changes in bone metabolism markers and lumbar BMD. The risks of DMAb-induced hypocalcemia are different between starting and switching from bone resorption inhibitors and bone formation promoters. Therefore, appropriate assessment before administration of DMAb, including pretreatment therapy as well as serum Ca and bone metabolic markers will help identify the risk of hypocalcemia following DMAb in combination with eldecalcitol. Our findings also showed that early change in serum Ca level after DMAb initiation could potentially predict the efficacy for therapy reaction.

Bone metabolism in response to oat bran consumption and jogging exercise in young males

Adopting a physically active lifestyle along with consumption of nutritional supplementation is a strategy for improving health-related quality of life. We aimed to investigate the combined effects of oat bran consumption and jogging exercise compared to oat bran consumption alone and jogging exercise alone on bone metabolism in young males. Forty-seven sedentary male university students with mean age 20.9 ± 1.7 years were recruited. They were randomly assigned into sedentary control (C), oat bran supplementation alone (OB), exercise alone (EX) and combined oat bran and exercise (OBEX) groups. The participants in OB and OBEX group consumed 18 g of oat bran powder with 3.6 g of β-glucan daily for 8 weeks. The participants in Ex and OBEx group performed jogging exercise with moderate intensity, i.e. 55–70% of their age-predicted HRmax, 30 min per day, 3 days per week for 8 weeks. Participants’ anthropometric parameters and bone metabolism markers were measured at pre- and post-intervention. Repeated measures ANOVA was performed for statistical analysis. In OB group, no significant changes in bone metabolism markers were observed. In EX group, there was a significant increase (p < 0.05) in carboxyterminal telopeptide of type 1 collagen (CTX-1). However, there were no significant changes in bone metabolism markers in OBEX group. Eight weeks of jogging exercise alone elicited significant effects on bone turnover marker in young sedentary males. Nevertheless, future studies with longer exercise duration and higher dosage of oat bran are warranted to investigate the combined effects of jogging exercise and oat bran consumption on bone metabolism markers in this population.

Serum bone alkaline phosphatase is a useful marker to evaluate lumbar bone mineral density in Japanese postmenopausal osteoporotic women during denosumab treatment.

A worldwide health concern, osteoporosis (OP), increases the risk of bone fracture and results in morbidity. This study examined whether the representative bone absorption marker serum tartrate-resistant acid phosphatase 5b (TRACP-5b) or bone formation marker bone alkaline phosphatase (BAP) could estimate primary OP status and denosumab efficacy in a real-world setting. We retrospectively enrolled 114 female postmenopausal primary OP patients in Japan. Values and percent changes in TRACP-5b, BAP, lumbar 1–4 bone mineral density (L-BMD), and total hip BMD (H-BMD) were assessed before treatment and at 4, 8, and 12 months of therapy to identify the correlations between the percent changes in bone metabolic markers and BMD. We also established two sets of subgroups based on the upper limits of reference values in Japan for serum: TRACP-5b (<420 mU/dL) and (≥420 mU/dL) and BAP (<14.5 µg/L) and (≥14.5 µg/L). Negative correlations were observed for the percent changes of TRACP-5b and H-BMD at 4 months (r=−0.3476) and 8 months (r=−0.3880), for the percent changes of BAP and H-BMD at 8 months (r=−0.3354), and for the percent changes of BAP and L-BMD at 12 months (r=−0.3186). We observed a significant difference between the subgroups for the percent changes of L-BMD at 8 months (p=0.013) and 12 months (p=0.004) in BAP values. These results suggest that TRACP-5b and BAP had negative correlations with BMD, and that BAP represented a useful serum marker to evaluate L-BMD during denosumab therapy for OP.

Correlating oxidative stress-related factors with bone metabolic markers in older adult male patients exhibiting degenerative osteoporosis in the high-altitude hypoxic area of China: study protocol for a non-randomized controlled trial

Background and objectives: Hypoxia is an important factor that affects bone formation and regulates bone growth. Therefore, many older adult patients living in high-altitude hypoxic areas exhibit osteoporosis. Oxidative stress-related hypoxia-inducible factors can induce abnormal expression of various factors including vascular endothelial growth factor (VEGF), insulin-like growth factor, and endothelin. However, it remains unclear whether these factors influence changes in bone metabolic markers. This study protocol aimed to investigate the correlation between oxidative stress-related factors and bone metabolic markers in older adult male patients with degenerative osteoporosis who reside in the high-altitude hypoxic area of China. Design: A prospective, single-center, non-randomized, controlled trial. Methods: One hundred and twenty older adult male patients with degenerative osteoporosis residing in the high-altitude area of China who receive treatment at the Affiliated Hospital of Qinghai University of China between January 2015 and February 2018 are being included in the osteoporosis group. One hundred and twenty healthy older adult males who concurrently received physical examination are being included in the control group. One day after admission, serum levels of hypoxia-inducible factor 1-alpha (HIF-1α), HIF-2α, VEGF, osteocalcin, and tartrate-resistant acid phosphatase 5b (TRACP 5b) were measured using an enzyme-linked immunosorbent assay. Bone mineral density in L1–4 segments, right femoral neck, and the greater trochanter of the femur was detected using dual-energy X-ray absorptiometry. Outcome measures: The primary outcome measure of this study is serum HIF-1α levels at 1 day after admission. Secondary outcome measures include serum levels of HIF-1α, HIF-2α, VEGF, osteocalcin, and TRACP 5b at 1 day after admission, as well as the correlation between serum levels of oxidative stress indicators (HIF-1α, HIF-2α, and VEGF) and bone metabolic markers (osteocalcin and TRACP 5b) at 1 day after admission. Discussion: Findings from this study aim to validate the correlation between oxidative stress-related factors and bone metabolic markers in older adult male patients with degenerative osteoporosis who reside in the high-altitude area of China. Ethics and dissemination: This study was approved by the Ethics Committee of the Affiliated Hospital of Qinghai University of China (approval No. QHY1402G). The study was performed in accordance with the Declaration of Helsinki. Participants are informed of the study protocol and procedures, and sign an informed consent. Participant recruitment, blood sampling, and data collection began in January 2015 and will be ended in February 2018. Outcome measure analysis and trial completion will be in March 2018. Results will be disseminated through presentations at scientific meetings and/or by publication in peer-reviewed journals. Trial registration: This trial was registered with the Chinese Clinical Trial Registry (registration number: ChiCTR-ROC-17012848).

Bone metabolism markers: Indicators of loading dose intravenous ibandronate treatment for bone metastases from breast cancer.

To investigate the changes in bone metabolism markers after second-line treatment with loading dose intravenous (i.v.) ibandronate in patients with bone metastases (BM) from breast cancer, 80 patients were enrolled in this study during January 2010 to April 2014. All the patients were treated with a second-line loading dose ibandronate for advanced breast cancer with BM and moderate-to-severe bone pain. Ibandronate (6mg) was intravenously administered on three consecutive days followed by maintenance treatment every 3-4weeks. Clinical data, including pain score, Karnofsky performance status (KPS) score, and changes in bone metabolism markers, were analyzed. Sixty-two patients were included in the final analysis. Compared with their pre-treatment scores, patients exhibited significantly increased KPS scores (P<.01) and a reduced dose of analgesic medication (oxycodone) (P<.01) after 3 and 6weeks' post-treatment. The levels of serum bone alkaline phosphatase (BAP), tartrate-resistant acid phosphatase (TRACP-5b), and cross-linked carboxy-terminal telopeptide of type I collagen (ICTP) were significantly reduced after 3 and 6weeks' post-treatment (P<.001). Aside from a few adverse events, no liver or renal toxicity was observed. Bone metabolism markers decreased by varying degrees after treatment with a loading dose of ibandronate in patients with BM from breast cancer. It might be convenient using bone metabolism markers to potentially evaluate the efficacy of bisphosphonates treatment for bone metastasis.

Effects of fluoride on insulin signaling and bone metabolism in ovariectomized rats

Fluoride is an essential trace element for the maintenance of bone health owing to its capacity to stimulate proliferation and osteoblastic activity that can lead to increased bone formation. However, excessive sodium fluoride (NaF) intake can impair carbohydrate metabolism thereby promoting hyperglycemia, insulin resistance, and changes in insulin signaling. Thus, this study aimed to evaluate the effect of chronic treatment with NaF in bone metabolism, insulin signaling, and plasma concentrations of glucose, insulin, tumor necrosis factor-α (TNF-α), osteocalcin (OCN), and fluoride in ovariectomized rats. Thirty-two ovariectomized Wistar rats were randomly distributed into two groups: Control (OVX-C) and those undergoing treatment with NaF (50mg F/L) in drinking water for 42days (OVX-F). Glucose and insulin levels were assessed, followed by homeostasis model assessment of insulin resistance (HOMA-IR). Akt serine phosphorylation was evaluated by western blotting. Plasma concentrations of TNF-α and OCN were evaluated by ELISA. The left and right tibia was collected for immunohistochemical and histomorphometric analysis, respectively. Chronic treatment with NaF promoted insulin resistance, decreased insulin signal, increased plasma concentration of insulin, fluoride, OCN and TNF-α, decreased trabecular bone area of the tibia, and caused changes in bone metabolism markers in ovariectomized rats. These results suggest the need for caution in the use of NaF for the treatment of osteoporosis, especially in postmenopausal woman.

Differences in vertebral, tibial, and iliac cancellous bone metabolism in ovariectomized rats.

Bone histomorphometry is usually performed on the iliac bone in humans and the tibia or vertebrae in rats. Bone metabolism differences among skeletal sites may be problematic when translating experimental results from rats to humans, but data on such differences in rats are lacking. Therefore, we examined the differences in bone structure and metabolism among skeletal sites using the lumbar vertebra (LV), tibia, and iliac bone obtained from ovariectomized or sham-operated rats preoperatively and at various times from 3days to 26weeks postoperatively. The trabeculae were thicker in the LV, where bone metabolism was less active than at other sites, and numerous fine trabeculae were observed in the tibia, where bone metabolism was more active. The iliac bone structure and metabolism were intermediate between those of the tibia and LV. Ovariectomy induced lower bone volume and higher bone metabolism in all skeletal sites, but the changes were greatest and occurred earliest in the tibia, followed by the iliac bone and then LV. Ovariectomy caused changes in bone metabolic markers, which occurred earlier than those in bone tissue. Activation frequency (Ac.f) increased after ovariectomy. At week 26 in ovariectomized rats, Ac.f was highest in the tibia (3.13N/year) but similar between iliac bone (0.87N/year) and LV (1.39N/year). Ac.f is reportedly 0.3-0.4N/year in the iliac bone of postmenopausal women, suggesting that bone turnover in rats is several times higher than in humans. The reference values reported here are useful for translating experimental results from rats to humans.