Primary Osteoporosis Patients Research Articles

The efficacy and safety of Gukang Capsule for primary osteoporosis: a systematic review and meta-analysis of randomized clinical trial.

Background: Gukang Capsule has been used as a complementary and alternative medicine (CAM) for the treatment of primary osteoporosis (POP) in China. The primary aim of this study was to assess the clinical effectiveness and safety of Gukang Capsule in POP patients. Methods: A systematic search was conducted across multiple academic databases including PubMed, Web of science, Cochrane Library, China National Knowledge Infrastructure, Chongqing VIP Information, and Wanfang database to identify randomized controlled trials investigating the Gukang Capsule in the treatment of POP. The screening process, data extraction, and assessment of methodological quality were conducted independently by two reviewers. Statistical analysis was performed using the Rev Man 5.3 software. Subgroup analysis was carried out through the combination of OPF. Subgroup analysis was performed according to whether OPF were combined. Stata 12.0 was used for sensitivity and bias analysis. Results: Nineteen studies were assessed that included 1804 participants. It was found that compared with the control group, the total effective rate (RR = 1.26, 95% CI, 1.20, 1.33), the Medical Outcomes Study Short-form 36 [RR = 1.26, 95% CI(1.20, 1.33)], the bone mineral density (BMD) of lumbar vertebra (SMD = 0.77, 95% CI, 0.48, 1.07), the BMD of femoral neck [SMD = 0.84, 95% CI(0.53, 1.14)], and the BMD of Ward's triangle (SMD = 0.64, 95% CI, 0.44, 0.85) of the Gukang Capsule experimental group were higher. Compared with the control group, the fracture healing time (SMD = -2.14, 95% CI, -2.45, -1.84), the bone specific alkaline phosphatase (BALP) levels in serum (SMD = -2.00, 95% CI, -2.83, -1.17), the tartrate resistant acid phosphatase 5b (TRACP-5b) levels in serum (SMD = -2.58, 95% CI, -3.87, -1.29) of the Gukang Capsule experimental group were lower. The bone glaprotein (BGP) levels in serum (SMD = -0.22, 95% CI, -1.86, 1.43) and the adverse events (RR = 0.80, 95% CI, 0.40, 1.63) of the experimental group and the control group have no difference. Conclusion: Gukang Capsule, as a CAM for the management of POP, exhibits the potential to enhance BMD and quality of life, expedite the healing time of OPF, diminish levels of BALP and TRACP-5b, and improve the total effective rate without increasing the adverse events. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023477774, PROSPERO CRD42023477774.

Determination of the Combined Effects of Asian Herbal Medicine with Calcium and/or Vitamin D Supplements on Bone Mineral Density in Primary Osteoporosis: A Systematic Review and Meta-Analysis.

To conduct a systematic review and meta-analysis to determine whether herbal medicine (HM) plus supplements such as calcium (Ca) or vitamin D (Vit.D) improves bone mineral density (BMD) compared to supplements alone in primary osteoporosis (OP) patients. We searched 5 databases for randomized controlled trials (RCTs) using HMs with supplements (Ca or Vit.D variants) as interventions for primary OP patients published until August 31, 2022. Meta-analysis using BMD score as the primary outcome was performed using RevMan 5.4 version. Risk of bias in the included studies was assessed useing RoB 2.0 tool. In total, 52 RCTs involving 4,889 participants (1,408 men, 3,481 women) were included, with average BMD scores of 0.690 ± 0.095g/cm2 (lumbar) and 0.625 ± 0.090g/cm2 (femoral neck). As a result of performing meta-analysis using BMD scores for all 52 RCTs included in this review, combination of HMs with Ca and Vit.D variants improved the BMD score by 0.08g/cm2 (lumbar, 38 RCTs, 95% CI: 0.06-0.10, p < 0.001, I2 = 97%) and 0.06g/cm2 (femoral neck, 19 RCTs, 95% CI: 0.04-0.08, p < 0.001, I2 = 92%)compared to controls. However, statistical significance of the lumbar BMD improvement disappeared after adjusting for potential publication bias. Our data suggest that combining of HM and supplements tends to be more effective in improving BMD in primary OP than supplements alone. However, caution is needed in interpretation due to the reporting bias and high heterogeneity among studies, and well-designed RCTs are required in the future.

Effects of kidney tonic herbs for primary osteoporosis: A systematic review and meta-analysis.

Primary osteoporosis (POP) is one of the most common orthopedic conditions with a high risk of fractures. Effective treatment of POP is crucial for reducing disability rates and improving quality of life. Kidney tonic therapy is a classical traditional Chinese medicine approach for treating POP. This study aims to provide a comprehensive and reliable assessment of the clinical evidence of kidney tonic herbs (KTH) in treating POP patients. An extensive literature search was conducted in 8 electronic databases from their inception through September 30, 2022, to evaluate the efficacy and safety of KTH for POP. We included 43 randomized controlled trials with 4349 participants. The qualified studies will be chosen and evaluated separately by 2 researchers. The primary outcome measure was bone mineral density (BMD) of lumbar. RevMan 5.3 and Stata 16 were used to carry out the meta-analyses. Our meta-analysis showed 29 studies with significantly increased lumbar BMD (mean difference [MD] = 0.06; 95% confidence interval [CI]; I2 = 98%, P = .003), 18 studies with noticeably higher femoral neck BMD (MD = 0.08; 95% CI; I2 = 98%, P = .0005), 6 studies with significantly increased femoral trochanter BMD (MD = 0.10; 95% CI; I2 = 97%, P = .002), 4 studies with noticeably higher ward's triangle BMD (MD = 0.13; 95% CI; I2 = 100%, P = .04), and 3 studies with noticeably higher distal radius BMD (MD = 0.06; 95% CI; I2 = 86%, P = .009). One study showed 12 falls and 8 fallers in the intervention group, 28 falls and 17 fallers in the control group at 36 months. 3 studies showed a significant difference in fracture incidence between the intervention group and the control group (95% CI: 0.15-0.81; I2 = 0%, P = .01). Additionally, the meta-analysis demonstrated that KTH offered superior pain relief (8 trials, n = 980; 95% CI: -1.05 to -0.74; I2 = 94%, P < .00001). Besides, KTH found no serious harmful effects. KTH may increase BMD and decrease the likelihood of fractures in POP patients. However, further research is necessary to investigate the effectiveness of KTH in reducing falls and fractures.

Association between Dysbiosis in the Gut Microbiota of Primary Osteoporosis Patients and Bone Loss.

In recent decades, gut microbiome research has experienced significant growth, driven by technological advances that enable quantifying bacterial taxa with greater precision. Age, diet, and living environment have emerged as three key factors influencing gut microbes. Dysbiosis, resulting from alterations in these factors, may lead to changes in bacterial metabolites that regulate pro- and anti-inflammatory processes and consequently impact bone health. Restoration of a healthy microbiome signature could mitigate inflammation and potentially reduce bone loss associated with osteoporosis or experienced by astronauts during spaceflight. However, current research is hindered by contradictory findings, insufficient sample sizes, and inconsistency in experimental conditions and controls. Despite progress in sequencing technology, defining a healthy gut microbiome across global populations remains elusive. Challenges persist in identifying accurate gut bacterial metabolics, specific taxa, and their effects on host physiology. We suggest greater attention be directed towards this issue in Western countries as the cost of treating osteoporosis in the United States reaches billions of dollars annually, with expenses projected to continue rising.

The assessment value of pathological condition of serum adiponectin and amylin in primary osteoporosis and its correlation analysis with bone metabolism indexes.

This paper explores the assessment value of pathological condition of serum adiponectin (APN) and amylin in primary osteoporosis (POP) and their correlation with bone metabolism indexes. From January 2019 to June 2021, 79 cases of POP patients were selected as the research objects. A test of the patients' bone density was conducted, and clinical grading of POP was via T value (normal, mild, moderate, severe). The analysis of the assessment value of pathological condition of serum APN and amylin for POP and their association with bone metabolism indexes in patients was performed. APN and amylin in patients were declined with POP's aggravation. APN of 5.15 μg/mL or less and amylin of 15.38 pmol/L or less were risk factors influencing the aggravation of pathological condition of POP (P< 0 .0 5). The area under the curve (AUC) of combined detection of APN and amylin to assess the severity of POP was elevated vs. alone test of amylin (P< 0.05). 25-hydroxyvitamin D (25-(OH) D) and total type 1 procollagen amino-terminal propeptide (t-PINP) in patients were descended with the aggravation of pathological condition of osteoporosis (P < 0.05). At the same time, no distinct differences were presented in the three groups of type I collagen hydroxyl terminal peptide b degradation product (β-CTX) and N-terminal osteocalcin (N-MID) (P> 0.05). APN, amylin, 25-(OH)D, β-CTX, and t-PINP were negatively linked with POP clinical grade (P< 0.05). APN and amylin were associated with 25-(OH) D, β-CTX, t-PINP (P< 0.05), and APN and amylin were not linked with N-MID (P> 0.05). Serum APN and amylin are provided with evaluation values for the severity of POP and are associated with bone metabolism in patients.

Curative Effect of Prebiotics/Probiotics Preparations Combined with Zoledronic Acid + Calcitriol Regimen on Patients with Primary Osteoporosis and Their Influences on Bone Metabolism Markers.

Objective To explore the curative effect of prebiotics/probiotics preparations combined with zoledronic acid + calcitriol regimen on patients with primary osteoporosis (POP) and the influences of prebiotics/probiotics preparations combined with zoledronic acid + calcitriol regimen on markers of bone metabolism. Methods 126 elderly hospitalized patients with POP in our hospital from January 2020 to December 2021 were divided into the control group (n = 63) and the observation group (n = 63) by the random number table method. The patients in the control group were treated with zoledronic acid and calcitriol, while the patients in the observation group were additionally treated with prebiotics/probiotics preparations. The clinical curative effect, bone metabolism, calcium-phosphorus metabolism indexes, intestinal floras, and cytokines levels before and via treatment between the two groups were compared. Results The total efficiency of the observation group was higher than that of the control group (P < 0.05). After treatment, the levels of bone gla protein (BGP), total propeptide of type I procollagen (PINP), and β-crosslaps (β-CTX) in both groups were lower than those before treatment, and the levels of BGP, total PINP, and β-CTX in the observation group were lower than those in the control group (P < 0.05). The levels of serum P in the both groups after treatment were lower than those before treatment, and the level of serum P in the observation group was lower than that in the control group (P < 0.05). The number of Escherichia coli after treatment in the two groups were less than that before treatment, and the number of Escherichia coli in the observation group was less than that in the control group (P < 0.05). The number of bifidobacteria and lactobacilli in the two groups after treatment were more than that before treatment, and the number of bifidobacteria and lactobacilli in the observation group were more than those in the control group (P < 0.05). After treatment, the levels of IL-6 and TNF-α in the two groups were lower than those before treatment, and the levels of IL-6 and TNF-α in the observation group was lower than those in the control group (P < 0.05). The levels of IGF-1 in the two groups after treatment were higher than those before treatment, and the levels of IGF-1 in the observation group was higher than that in the control group (P < 0.05). Conclusion The response rate of prebiotics/probiotics preparations combined with zoledronic acid + calcitriol regimen is high in the treatment of POP patients, which ameliorates bone metabolism and intestinal floras, and suppresses cytokines release in patients with POP.

Bone Marrow Mesenchymal Stem Cell-Exosomes (BMSC-ExO) Promote Osteogenic Differentiation In Vitro and Osteogenesis In Vivo by Regulating miR-318/Runt-Related Transcription Factor 2 (RUNX2)

Primary osteoporosis (PMOP) is characterized by bone mass reduction and bone microstructure destruction, increased bone fragility and prone to fracture, which is partially caused by ovarian dysfunction and decreased estrogen content. Bone marrow mesenchymal stem cell exosomes (BMSC-ExO) can improve PMOP. In this study, BMSC-EXO was used to study the role and function of miR-318 and Runx2 in PMOP. Human osteogenitor cells were isolated from PMOP patients with primary osteoporosis. After BMSC-exo treatment, miR-318 and Runx 2 level was tested by RT-qPCR and Western blot. In addition, mice in OVX group were treated with BMSC-ExO (bilateral ovaries were removed) to observe the effect of BMSC-ExO on bone tissue. Our results showed that BMSC-exo treatment significantly decreased miR-318 level, upregulated RUNX2 expression and increased ALP activity. In addition, BMSC-exo administration ameliorated the declined bone mass and bone formation in osteoporotic femurs in OVX mice. In conclusion, BMSC-Exo enhances Runx2 levels by down-regulation of miR-318, thereby promoting osteogenic differentiation of osteogenitor cells, providing new potential therapeutic targets for treating PMOP.

Features of mandibular cortical bone morphology in osteoporotic fracture patients.

The diagnostic criteria for osteoporosis are based on the bone mineral density (BMD) level in the lumbar spine and femur bone. Patients with osteoporotic fractures were diagnosed with osteoporosis. While systemic BMD and mandibular cortical bone morphology are correlated, this has not been studied in patients with a history of osteoporotic fractures. Therefore, purpose of this study was researching the mandibular cortical bone morphology in patients with osteoporotic fractures. The subjects were 55 female and 20 male patients with osteoporotic fractures. Patients were divided into 30 primary osteoporosis patients and 45 secondary osteoporosis patients according to the medical history. Patients underwent BMD and panoramic radiography examinations during orthopedic treatment for fractures. A dual-energy X-ray absorptiometry system was used to measure BMD. Mandibular cortex index (MCI) and mandibular cortex width (MCW) were evaluated using machine-learning measurement software. In the analysis of MCI, the ratio of class 2 and 3 was 73% of both primary osteoporosis and secondary osteoporosis. The average MCW was 2.19mm for primary osteoporosis and 2.30mm for secondary osteoporosis. The sensitivity values by MCI and MCW were 73% and 76% for both primary and secondary osteoporosis, which were similar detection powers. In addition, the false-negative rates by MCI and MCW were 27% and 24%. We suggested that MCI and MCW are indicators of osteoporotic conditions in patients with primary and secondary osteoporosis. Our results show that MCI and MCW are non-inferior to the sensitivity values for lumbar BMD in patients with osteoporotic fractures.

Effect of Denosumab in Primary Osteoporosis Patients According to Their Bisphosphonate Response

Effect of Denosumab in Primary Osteoporosis Patients According to Their Bisphosphonate Response

The characteristics of primary osteoporosis patients with sarcopenia

The characteristics of primary osteoporosis patients with sarcopenia

Acupoint injection treatment for primary osteoporosis: a systematic review and meta-analysis of randomized controlled trials.

Acupoint injection has currently received increasing attention as a treatment for primary osteoporosis (POP), This study aimed to evaluate the efficacy and safety of acupoint injection as a clinical treatment for POP. Randomized controlled trials (RCTs) of acupoint injection compared with conventional non-acupoint injection for POP were identified in searches of seven databases from their inception to March 2019. All data were assessed and extracted by two authors independently. The risk of bias assessment recommended by the Cochrane Collaboration was used to assess the quality of the selected studies. RevMan 5.3 was used to conduct meta-analysis for the efficacy and safety of acupoint injection. Five trials with 337 patients (aged 45-86 years) with bone mineral density (BMD) ≤2 SD were included in our meta-analysis. The results showed that, compared with conventional intramuscular injection, acupoint injection significantly increased the BMD [mean difference (MD) =0.02; 95% CI, 0.01 to 0.03, P<0.00001]. Subgroup analysis indicated that acupoint injection significantly improved lumbar BMD (MD =0.02; 95% CI, 0.01 to 0.03, P<0.00001) but did not reduce the pain score (SMD =-2.29, 95% CI, -6.81 to 2.23, P>0.05). Individuals results showed that acupoint injection improved biochemical indicators, such as NBAP, IGF-I and reduced CTX and leptin levels. While the risk of bias was high in all five trials. This meta-analysis and systematic review suggests that acupoint injection improves BMD and some biochemical indicators in POP patients compared with the effects of conventional intramuscular injection. However, due to the high risk of bias in all the trials reviewed, the evidence remains inconclusive and future research will be required with improved methodological quality.

Study of twice-weekly injections of Teriparatide by comparing efficacy with once-weekly injections in osteoporosis patients: the TWICE study

SummaryA 48-week, multicenter, randomized, double-blind, double-dummy, active-controlled, non-inferiority trial (the TWICE study) conducted in Japanese primary osteoporosis patients with a high risk of fractures demonstrated that a 28.2-μg twice-weekly regimen of teriparatide can provide comparable efficacy to a 56.5-μg once-weekly regimen of teriparatide, while also improving safety.IntroductionWhile a 56.5-μg once-weekly regimen of teriparatide has high efficacy for osteoporosis, treatment continuation rates are low, with one of the major causes being adverse drug reactions such as nausea or vomiting. The TWICE study was therefore conducted to investigate whether a twice-weekly regimen with 28.2-μg teriparatide can provide comparable efficacy to the 56.5-μg once-weekly regimen while improving safety.MethodsA 48-week, multicenter, randomized, double-blind, double-dummy, active-controlled, non-inferiority trial was conducted in Japan. Patients with primary osteoporosis aged ≥ 65 years at high risk of fractures (n = 553) were randomly allocated to the 28.2-μg twice-weekly group (n = 277) or the 56.5-μg once-weekly group (n = 276). The primary endpoint was the percentage change in lumbar spine (L2–L4) bone mineral density (BMD) at final follow-up.ResultsThe percentage changes in lumbar spine (L2–L4) BMD at final follow-up in the 28.2-μg twice-weekly and 56.5-μg once-weekly groups were 7.3% and 5.9%, respectively; the difference (95% confidence interval [CI]) in percentage change was 1.3% (0.400–2.283%). Since the lower limit of the 95% CI was above the pre-specified non-inferiority margin (− 1.6%), non-inferiority of the 28.2-μg twice-weekly group was demonstrated. Adverse drug reactions were significantly less frequent in the 28.2-μg twice-weekly group (39.7% vs 56.2%; p < 0.01); the incidence of major adverse drug reactions was lower, and the number of subjects who discontinued due to adverse drug reactions was less in the 28.2-μg twice-weekly group.ConclusionsA 28.2-μg twice-weekly regimen of teriparatide can provide comparable efficacy to a 56.5-μg once-weekly regimen while improving safety.Clinical trial registrationJapicCTI-163477.

Efficacy of 4-year denosumab treatment alone or in combination with teriparatide in Japanese postmenopausal osteoporotic women

Purpose: This extended randomized prospective study aimed to compare the 4-year clinical outcomes of denosumab treatment alone or in combination with teriparatide in treatment-naïve postmenopausal Japanese patients with osteoporosis.Methods: Between July 2013 and December 2016, 30 eligible women from our previous study were enrolled. After newly adding 17 randomly assigned patients, 47 patients were classified into the denosumab alone group (denosumab group, n = 22) or denosumab plus teriparatide group (combination group, n = 25). Serum bone-specific alkaline phosphatase (BAP), serum tartrate-resistant acid phosphatase (TRACP)-5b, urinary cross-linked N-terminal telopeptide of type I collagen (NTX), and bone mineral density (BMD) of the lumbar 1–4 vertebrae (L-BMD) and bilateral total hips (H-BMD) were determined at the first visit and at regular time points up to 48 months of treatment to determine percentage changes.Results: BAP was significantly decreased from baseline in both groups from 24 to 48 months, with significant differences at all time points between the groups. TRACP-5b and urinary NTX were comparably decreased at every time point in both groups versus pretreatment levels. L-BMD was significantly more increased by combination therapy over denosumab alone at 24 and 30 months (21.1% increase vs. 14.2% increase at 48 months). There were no significant differences in H-BMD between the groups, although levels tended to be higher in the combination group throughout the study period (9.7% increase vs. 6.8% increase at 48 months).Conclusion: Long-term denosumab and teriparatide combination therapy represents an effective treatment option for primary osteoporosis patients with low L-BMD.

Combining information from multiple bone turnover markers as diagnostic indices for osteoporosis using support vector machines

Context: Osteoporosis (OP) is a progressive systemic bone disease. Dual-energy X-ray absorptiometry (DXA) is routinely employed and is considered the gold standard method for the diagnosis of OP.Objective: We aimed to investigate the potential use of combined information from multiple bone turnover markers (BTMs) as a clinical diagnostic tool for OP.Materials and methods: A total of 9053 Chinese postmenopausal women (2464 primary OP patients and 6589 healthy controls) were recruited. Serum levels of six common BTMs, including BAP, BSP, CTX, OPG, OST and sRANKL were assayed. Models based on support vector machine (SVM) were constructed to explore the efficiency of different combinations of multiple BTMs for OP diagnosis.Results: Increasing the number of BTMs used in generating the models increased the predictive power of the SVM models for determining the disease status of study subjects. The highest kappa coefficient for the model with one BTM (BAP) compared to DXA was 0.7783. The full model incorporating all six BTMs resulted in a high kappa coefficient of 0.9786.Conclusion: Our findings showed that although single BTMs were not sufficient for OP diagnosis, appropriate combinations of multiple BTMs incorporated into the SVM models showed almost perfect agreement with the DXA.

The impact of switching once-weekly teriparatide to denosumab in osteoporosis patients

BackgroundIt has been reported that switching from daily (d) teriparatide (TPTD) to denosumab (DMAb) is effective for severe osteoporosis patients. However, there have been no reports about switching from weekly (w) TPTD to DMAb in patients with osteoporosis. Once-weekly 56.5-μg TPTD treatment increases bone mineral density (BMD) and reduces fracture events. The objective of the current retrospective study was to elucidate the impact of switching w-TPTD to DMAb in patients with osteoporosis. MethodsIn this study, 40 patients were treated with w-TPTD for 18 months and then switched to DMAb for 18 months. The sample included 2 men and 38 women with a mean age of 74.5 (60–85) years. Twenty-five subjects had primary osteoporosis, and 15 had secondary osteoporosis. The mean number of osteoporotic vertebral fractures was 4.1. Serum bone turnover markers and BMD were evaluated every 6 months. ResultsBone alkaline phosphatase (BAP) and tartrate resistant acid phosphatase 5b (TRACP5b), markers of bone formation and resorption respectively, were not significantly different in w-TPTD subjects at 18 months compared with those at baseline (p > 0.05), but BAP and TRACP5b in subjects treated with DMAb were significantly lower at 36 months compared with those at baseline (p < 0.05). BMD of the lumbar spine (LS), femoral neck (FN), and total hip (TH) increased by 12.3%, 2.5%, and 2.2% by 36 months with DMAb treatment, significantly higher than at baseline (p < 0.05). Changes in BMD of FN and TH in primary osteoporosis patients were significantly higher than in secondary osteoporosis patients at 18 months (w-TPTD) and 36 months (DMAb, p < 0.05). ConclusionBMD significantly increased in osteoporosis patients switched from w-TPTD to DMAb. However, the impact of switching from w-TPTD to DMAb in secondary osteoporosis patients was not as great as in primary osteoporosis patients at the view points of changes in BMD of FN and TH.

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.

Comparison of the effects of denosumab with either active vitamin D or native vitamin D on bone mineral density and bone turnover markers in postmenopausal osteoporosis

Osteoporosis is a worldwide health concern. Although treatment with denosumab plus the active vitamin D alfacalcidol has been found to improve femoral neck (FN) and distal forearm bone mineral density (BMD), there have been no reports on the efficacy or adverse effects of denosumab plus eldecalcitol (ELD) in primary osteoporosis patients. Fifty-six treatment-naïve post-menopausal women with primary osteoporosis were recruited and divided into denosumab plus native vitamin D or denosumab plus ELD. Ultimately, 26 subjects in the native vitamin D group and 24 in the ELD group were analyzed. Lumbar and total hip BMD significantly increased in both groups. However, there was no significant difference in the percent increase of lumbar and total hip BMD between two groups. FN-BMD was significantly increased from 6 to 12 months in the ELD group compared with baseline. This study revealed that combination therapy with denosumab and ELD could improve FN-BMD more effectively than denosumab plus native vitamin D. Thus, the addition of ELD may enhance the effects of denosumab treatment for primary osteoporosis.

Design of a Multicenter, Randomized, Open Label, Parallel Group Study to Evaluate the Efficacy of Loxoprofen on Acute-Phase Reactions in Japanese Primary Osteoporosis Patients Treated with Zoledronic Acid

Treatment of osteoporosis with once-yearly zoledronic acid was approved in September 2016 in Japan. Like other bisphosphonates, zoledronic acid causes acute-phase responses (APRs), which are more severe in Asian populations than in multinational populations. The aim of this multicenter, randomized, open label, parallel group study is to investigate the incidence of APRs in Japanese patients with primary osteoporosis in real clinical settings, and to test the hypotheses that APRs are suppressed by administering one of the most commonly used nonsteroidal anti-inflammatory drugs in Japan, loxoprofen, immediately after the treatment with zoledronic acid, and the incidence of APRs in patients with prior history of treatment with bisphosphonate is lower than that in naive patients. A total of 400 patients aged 60 or older were randomly allocated to a zoledronic acid plus loxoprofen group or zoledronic acid group on a 1:1 basis. After the treatment, patients were observed for 7 days, during which patients will record APRs for the first 3 days, and body temperature and drugs taken for 7 days. Primary endpoints are incidence of APRs and increase in body temperature, and secondary endpoints are relationship between prior treatment for osteoporosis in the past 3 years versus incidence of APRs, and that versus a change in body temperature. Results supporting the hypotheses will indicate that APRs are manageable with loxoprofen, which patients likely already have, and the APRs will develop less frequently and be less severe in the following years, despite the high risk of APRs in Japanese patients.

Is denosmab really effective and safe in the care of CKD-MBD?

The authors of Freedom study enrolling primary osteoporosis patients argued that the anti-fracture effect of denosmab is not dependent on baseline estimated glomerular filtration rate(eGFR)by showing the non-significant interaction term between treatment and CKD stage. However, given disproportionate numbers of patients in each subgroup(4069, 2817, and only 73 patients, in CKD stage 2, 3, and, 4, respectively), this study seems to lack the statistical power to reach a definite conclusion on the effect modification by CKD stage. Truly, the serum concentration of infused denosmab in patients with CKD stage 4 is equivalent to that in patients without CKD, the risk of developing life-threatening or prolonged hypocalcemia is huge even under active vitamin D therapy in this population. In hemodialysis patients, this drug is relatively safer because each dialysis session delivers calcium into the circulation 3 times a week. However, even with concomitant administration of massive active vitamin D, the increase of intact PTH levels greater than 1000 pg/mL by this agent is not rare. In other words, this drug worsens secondary hyperparathyroidism. Moreover, reportedly, calcium and active vitamin D administered to avoid hypocalcemia can lead to ectopic calcification especially under the low bone turnover induced by this agent. In fact, transient hypercalcemia often follows hypocalcemia by the inevitable calcium supplementation.

Analysis of acute phase side-effects of diphosphonate treatment in elderly patients with primary osteoporosis

Objective To investigate the acute phase adverse effects and influencing factors of adverse effects of diphosphonate treatment in the elderly patients with primary osteoporosis. Methods A total of 208 patients[male 25 patients, female 183 patients, age 60~93 with a average of (75.51±7.73)years]with primary osteoporosis were selected from 1 Jan 2012 to 30 Nov 2015, admitted to Department of Geriatrics. According to the serious condition of osteoporosis and willingness of patients, 208 patients were divided into zoledronic acid treatment group, alendronate treatment group, and pamidronic acid group, and received corresponding diphosphonate treatment. All kinds of adverse reactions of diphosphonate in each treatment group were closely to be observed after administration of diphosphonate in 3 days and 7 days. Results The incidence rate of adverse reactions in the zoledronic acid treatment group (59/134, 44.03%; 60/134, 44.78%) was obviously higher than that in the alendronate treatment group (1/57, 1.75%; 1/57, 1.75%), and the pamidronic acid group (3/17, 17.65%; 3/17, 17.65%) after treatment of diphosphonate in three and seven days (P 0.05). There were three patients suffering from severe acute kidney injure (AKI) and three patients suffering from hypokalemia in the 134 patients treatment with zoledronic acid. Conclusions There are obvious differences in the incidence rate of acute phase adverse reactions in the osteoporosis patients who received different treatment policy (P<0.05). The safety issues in the kidney function and electrolyte abnormality (such as hypokalemia) should be paid much enough attention in the primary osteoporosis patients who receive zoledronic acid treatment. Key words: Osteoporosis/DT; Diphosphonates/AE