Efficacy of Yigu® versus Aclasta® in Chinese postmenopausal women with osteoporosis: a multicenter prospective study

Summary Zoledronic acid (ZOL) is a therapy inhibiting bone resorption. In this study, generic ZOL (Yigu®) showed its clinical efficacy consistency with original ZOL (Aclasta®) in Chinese postmenopausal women with osteoporosis. This study provides a practical basis for the application of Yigu® in Chinese population. Introduction Yigu® has been approved its bioequivalence to Aclasta®. However, the clinical efficacy and safety of Yigu® have not been evaluated yet. Here, we compared the effectiveness and safety between Yigu® and Aclasta® in Chinese postmenopausal women with osteoporosis and assessed the efficacy of intravenous infusion of ZOL. Methods This was a randomized open-label, active-controlled study in postmenopausal women with osteoporosis of 14 clinical centers in China. Postmenopausal women with osteoporosis were recruited and randomized to receive a single infusion of 5 mg Yigu® or Aclasta®. The primary endpoint was the percentage change in bone mineral density (BMD) at lumbar spine after 12 months of treatment and was assessed for equivalence. The secondary endpoint was the percentage change in BMD at proximal femur after 12 months. Additional secondary endpoints were percentage changes in BMD at the above sites after 6 months of treatment and changes in bone turnover biomarkers during ZOL treatment. Safety was also evaluated and compared between two groups. Results A total of 458 postmenopausal women with osteoporosis were enrolled (n = 227, Yigu®; n = 231, Aclasta®). The mean percentage change in the BMD had no statistical difference at the lumbar spine (5.32% vs 5.18%), total hip (2.72% vs 2.83%), and femoral neck (2.37% vs 2.81%) between Yigu® and Aclasta® groups after 12 months of treatment. The mean difference of BMD change at the lumbar spine after 12 months between two groups was 0.15% (95% CI: − 0.71 to 1.00, equivalence margin: − 1.5%, 1.5%), demonstrating the treatments were equivalent. Meanwhile, the decreases in the P1NP and β-CTX showed no difference between two groups after 14 days and 6 and 12 months of treatment. As regards the whole sample, BMD significantly increased after 12 months of treatment. Also, serum C-terminal telopeptide of type 1 collagen (β-CTX) and procollagen 1 N-terminal peptide (P1NP) significantly decreased at each visit period. The overall adverse events were comparable and quite well between two groups. Conclusion Intravenous infusion of zoledronic acid achieved the potent anti-resorptive effects which led to significant increase in BMD of Chinese postmenopausal women with osteoporosis. Yigu® was equivalent to Aclasta® with respect to efficacy and safety.

Expression of angiogenic markers in jawbones and femur in a rat model treated with zoledronic acid

Objectives This study aimed to investigate the gene expression of angiogenic marker in surgically treated jawbones and femur on a rat model administrated with zoledronic acid. Results No soft tissue fenestration or bone exposure was found in femur. Delayed soft tissue healing was found in both ZA group (3 in mandible, 4 in maxilla) and control group (1 in mandible, 2 in maxilla), while exposed bone was found only in the ZA group (1 in maxilla, 2 in mandible). RT-PCR analysis demonstrated no significant difference in gene expression of angiogenetic markers between ZA-treated and control groups in femur and mandible. In the maxilla, the expression of VEGFA and VEGFR-2 in medium-term ZA group was significantly down-regulated compared with that in the control. The ZA treatment does not change significantly the expression of the angiogenic factors in femur and mandible, but significantly downregulates the expression in maxilla in this rat model. The angiogenesis inhibition may contribute to the development of MRONJ but does not play a key role.

Role of zoledronic acid in treatment of osteoporosis and prevention of fractures

Introduction. One of the causes of primary disability and high mortality, among patients with osteoporosis, are fractures that occur with minimal trauma, as a rule, it is a fall from the height of one’s own height. The final link in the chain of preventive measures to reduce the frequency of osteoporosis and fractures on its background is the introduction of pharmacological correction of bone deficiency into the practical activity of an orthopedic traumatologist. Currently, there are several drugs that can change the disturbed metabolism. For example, the use of zoledronic acid significantly reduces the risk of fractures.Aim: to study the effect of zoledronic acid on bone mineral density in patients with osteoporosis complicated by a fracture of proximal end of the femur.Materials and methods. In a prospective cohort study, 14 patients received zoledronic acid for 2 years.Results. When comparing BMD L2-L4, it was revealed that a year after the start of treatment, its increase relative to the baseline value was 4.6%, but was statistically insignificant (0.86 ± 0.078 g/cm2 versus 0.90 ± 0.08 g/cm2, p > 0.05). After 2 years of treatment, the BMD of this segment increased, relative to the baseline values, by 12% and the differences became statistically significant (0.86 ± 0.078 g/cm2 compared to 0.97 ± 0.076 g/cm2, p < 0.05). The increase in BMD for the second year of treatment by 6% was statistically significantly different from the increase for the first year of treatment (0.90 ± 0.08 g/cm2 compared to 0.97 ± 0.076 g/cm2, p < 0.05).A comparative analysis of the basic units of the IPC hip after 1 and 2 years of treatment did not reveal significant differences: 0.7075 ± 0.046 g/cm2 compared to 0.7079 ± 0.034 g/cm2 and 0.70751 ± 0.046 g/cm2 compared to 0.6630 ± 0.97 g/cm2, p > 0.05. In any case, for 2 years not marked new vertebral body fractures. Only one patient had a fracture of the radius in the distal third. The quality of life, after 2 years, significantly improved on the scale of “habitual daily activities” (p = 0.007), decreased indicators on the scale of “anxiety” and “depression” (p > 0.05).Discussion. The study confirmed that even in the presence of pronounced bone loss, pharmacological correction of impaired remodeling reduces the risk of new fractures and improves the quality of life.Conclusion. Pharmacotherapy with zoledronic acid, in our study, confirmed its effectiveness in the treatment of osteoporosis.

Men’s health and osteoporosis: modern treatment and prevention options

Osteoporosis (OP) has traditionally been seen as a pathology that mainly occurs in postmenopausal women and elderly men, and until recently, the problem of this disease among males has not been given sufficient priority. At the moment, however, OP in men is widely acknowledged to be an important issue of modern health care. Given the etiological and pathogenetic characteristics, two categories of OP have been identified: primary and secondary. In the structure of male OP, the secondary category of OP accounts for up to 40-60 % of all cases. Hypogonadism is one of the common causes of bone loss in men. Initially, males develop a larger bone mass compared to women and, accordingly, greater bone strength. Men over the age of 50 do not undergo rapid bone mass loss, as women do after menopause, and the bone mass decreases more gradually, in a linear manner. With ageing, the trabecular number (Tb.N) in men are relatively maintained with underlying more pronounced thinning of Tb. N associated with decreased osteoblast-forming activity. Although the prevalence of OP among men is significantly lower than among women, the clinical consequences of OP in men are of a great importance. The primary strategy of the anti-osteoporotic therapy is to prevent OP and low-traumatic fractures. According to the current guidelines for the treatment of OP in men, bisphosphonates (BP) are the drugs of choice. Zoledronic acid is a highly effective nitrogen-containing BP, the first drug to be injected once a year. Intravenous injection of zoledronic acid is as effective in reducing the risk of fractures in men as in women.

Characteristics Associated with Acute-Phase Response following First Zoledronic Acid Infusion in Brazilian Population with Osteoporosis

We aimed to evaluate characteristics associated with acute-phase response (APR) following first zoledronic acid infusion in a Brazilian cohort. This retrospective cohort study enrolled all adults with osteoporosis who underwent a first zoledronic acid infusion at our centre between June 2015 and June 2019. Clinical demographics (age, sex, diabetes, smoking, body mass index, and previous oral bisphosphonate use) and laboratory data (calcium, parathyroid hormone, renal function, and serum 25-hydroxyvitamin D and carboxy-terminal crosslinked telopeptide of type 1 collagen [CTX], both before and after infusion) were compared between patients with and without APR. We evaluated association magnitude between the presence of APR and clinical variables through logistic regression. This study enrolled 400 patients (women, 80%). APR was observed in 24.5% (n = 98) of patients. The mean symptom duration in days was 3.5 ± 2.8. Patients with APR were younger (67 ± 12 vs. 71 ± 11 years; p = 0.001 ), used oral bisphosphonates less frequently (34% × 50%; p = 0.005 ), and had greater baseline CTX (0.535 ng/mL [0.375, 0.697] × 0.430 [0.249, 0.681]; p = 0.03 ) and ΔCTX (−69 [−76; −50] × −54 [−72; −23]; p = 0.002 ) than those without APR. The other variables were similar between the groups. Only ΔCTX was associated (OR, 0.62; 95% CI 0.41–0.98) with APR after accounting for age and bisphosphonate use. APR occurred in 24.5% of the cohort. Younger age and absence of prior oral bisphosphonate use were associated with APR following first zoledronic acid infusion. APR was associated with ΔCTX (but no other variables) after adjusting for these factors.