Drug efficacy and safety of denosumab, teriparatide, zoledronic acid, and ibandronic acid for the treatment of postmenopausal osteoporosis: a network meta-analysis of randomized controlled trials.

Authors: W-Y Wang, L-H Chen, W-J Ma...

OBJECTIVE

This study aims to compare the efficacy and safety of denosumab, teriparatide, zoledronic acid, and ibandronic acid for the treatment of women with postmenopausal osteoporosis.

MATERIALS AND METHODS

Randomized controlled trials (RCTs) were searched in Medline, Embase, and Cochrane up to April 2022. Statistical analysis was performed using R 4.1.3 software, and quality evaluation was conducted using Review Manager 5.3.

RESULTS

51 RCTs containing 39,095 patients met our selection criteria. The efficacy results indicated that teriparatide was more effective than ibandronic acid in reducing vertebral fractures [relative risk (RR) = 0.536; 95% confidence interval (CI) (0.266, 0.998)]. Denosumab [mean difference (MD) = -4.19; 95% CI (-8.03, -0.355)] and teriparatide [MD = 4.64; 95% CI (1.60, 7.72)] showed better efficacy than ibandronic acid in improving spine bone mineral density (BMD). Denosumab showed better efficacy than teriparatide in improving radius BMD [MD = -4.14; 95% CI (-6.72, -1.54)], hip bone mineral density (BMD) [MD = -2.01; 95% CI (-3.80, -0.162)], and one-third radius BMD [MD = -3.63; 95% CI (-7.04, -0.151)]. Denosumab was associated with the greatest benefit in increasing radius BMD [the surface under the cumulative ranking curve area (SUCRA) = 0.999], hip BMD [surface under the cumulative ranking curve area (SUCRA) = 0.979], femoral neck BMD (SUCRA = 0.971), one-third radius BMD (SUCRA = 0.994) and preventing vertebral fractures (SUCRA = 0.806). Teriparatide was associated with the greatest benefit in preventing non-vertebral fractures (SUCRA = 0.927) and improving spine BMD (SUCRA = 0.899). The safety results indicated that teriparatide was safer than zoledronic acid regarding the risk of adverse events [RR = 0.958; 95% CI (0.919, 0.988)]. Teriparatide was associated with the greatest benefit in preventing adverse events (SUCRA = 0.908) and serious adverse events (SUCRA = 0.813).

CONCLUSIONS

Our current results suggested that when considering both safety and efficacy, denosumab or teriparatide might be a better choice for women with postmenopausal osteoporosis.

Topics: Female; Humans; Denosumab; Ibandronic Acid; Osteoporosis, Postmenopausal; Randomized Controlled Trials as Topic; Spinal Fractures; Teriparatide; Zoledronic Acid

PubMed: 37750653
DOI: 10.26355/eurrev_202309_33586

Authors: Judith Everts-Graber, Harald Bonel, Daniel Lehmann...

UNLABELLED

This registry-based study of 3068 patients with osteoporosis compared the anti-fracture effectiveness of denosumab versus bisphosphonates. Denosumab was associated with significantly greater risk reduction than alendronate or ibandronate for vertebral and any fractures. No difference in fracture risk reduction was found between zoledronate and denosumab.

PURPOSE

To analyse the fracture risk of patients with osteoporosis receiving bisphosphonates or denosumab in a real-world setting.

METHODS

This registry-based cohort study evaluated patients taking denosumab, bisphosphonates or both sequentially. Fractures were analysed using rates, rate ratios and hazard ratios (HR), including both therapies as time-varying co-variates. Fracture risk hazards were adjusted (aHR) for baseline T-Scores and trabecular bone score (TBS) and were additionally analysed with inverse probability treatment weighting.

RESULTS

A total of 3068 patients (89% female; median age at treatment onset, 69 years [63 to 76]) received denosumab (median duration 2.8 years, [2.2 to 4.7]), bisphosphonates (3.4 years, [2.1 to 5.7]) or both sequentially. Thus, 11,078 subject-years were assessed for bisphosphonates (41% alendronate, 36% ibandronate, 23% zoledronate) and 4216 for denosumab. Moreover, 48,375 subject-years were observed before treatment onset, in addition to 2593 years of drug holidays. A total of 1481 vertebral fractures (435 under therapy), 1508 non-vertebral fractures (499 under therapy) and 202 hip fractures (67 under therapy) occurred after age 50. The risks of vertebral, non-vertebral and hip fractures were significantly lower under all bisphosphonates, denosumab and drug holidays than before treatment onset (all p < 0.001). After adjusting for age, baseline T-scores and TBS, denosumab was associated with lower risk than alendronate or ibandronate for vertebral fractures (aHR 0.47 (0.35 to 0.64) and 0.70 [0.53 to 0.91], p < 0.001 and p = 0.009, respectively) and any fractures (aHR 0.62 [0.51 to 0.76] and 0.77 [0.64 to 0.92], p < 0.001 and p = 0.004). With propensity weighting, denosumab was associated with a lower hip fracture risk compared to alendronate (HR 0.54 [0.29 to 0.98], p = 0.044). No difference in fracture risk reduction (vertebral, non-vertebral or hip) was found between zoledronate and denosumab.

CONCLUSIONS

When adjusting for disease severity, denosumab was associated with significantly greater risk reduction than alendronate and ibandronate for vertebral fractures. No difference in fracture risk reduction was found between zoledronate and denosumab.

Topics: Humans; Female; Aged; Middle Aged; Male; Alendronate; Ibandronic Acid; Zoledronic Acid; Denosumab; Cohort Studies; Bone Density Conservation Agents; Diphosphonates; Osteoporosis; Hip Fractures; Spinal Fractures; Registries; Osteoporosis, Postmenopausal

PubMed: 37493978
DOI: 10.1007/s00198-023-06863-y

Effects of zoledronic acid and ibandronic acid on renal functions and calcium, phosphorus and alkaline phosphatase levels in breast cancer patients with bone metastases: a retrospective analysis.

Authors: Evren Fidan, Bulent Yildiz, Halil Kavgaci...

AIM OF THE STUDY

Bone is a common site of metastasis in patients with breast cancer. Skeletal complications associated with bone metastasis are commonly treated with bisphosphonates. However, there are a number of side-effects associated with these, such as renal failure, hypocalcemia and osteonecrosis of the jaw. We aimed to determine the effects of ibandronic and zoledronic acid on serum creatinine (SCr), calcium (Ca), phosphorus (P), alkaline phosphatase (ALP) and estimated glomerular filtration rates (eGFR). The objective was to determine the safety of these bisphosphonates, especially zoledronic acid.

MATERIAL AND METHODS

Forty-one patients diagnosed with breast cancer (all with bone metastasis) were enrolled. We retrospectively evaluated bisphosphonate type, duration of treatment, infusion time and the parameters SCr, Ca, P, ALP and eGFR.

RESULTS

Nineteen patients were included in the zoledronic acid group and 22 in the ibandronic acid group. Mean age in the ibandronic acid group was 53.27 ±11.01, and 53.26 ±9.98 in the zoledronic acid group. Median duration of administration in the ibandronic acid group was 11 (7-37) months, and 10 (7-57) months in the zoledronic acid group. SCr levels did not change significantly during the study period. Pre- and post-treatment Ca levels were also unchanged, but serum ALP levels in the ibandronic acid group and P levels in the zoledronic acid decreased after the final administration; eGFR was unchanged by the end of the study.

CONCLUSIONS

Zoledronic and ibandronic acid are safe modalities in the treatment of skeletal events in breast cancer patients with bone metastasis.

PubMed: 23788873
DOI: 10.5114/wo.2012.28799

Authors: Y Kucukzeybek, G Gorumlu, E Cengiz...

Over 80% of patients with advanced breast and prostate cancer ultimately develop bone metastases. Ibandronic acid has proven efficacy for treatment of bone metastasis secondary to breast cancer. This study was designed to investigate the cytotoxic and apoptotic effects of ibandronic acid on hormone- and drug-refractory prostate carcinoma DU-145 and human breast cancer MCF-7 cell lines. Cytotoxicity was evaluated using an XTT cell proliferation kit, and apoptosis was assessed by enzyme-linked immunosorbent assay (histone-DNA fragmentation) and measurement of caspase 3/7 activity. With increasing concentrations of ibandronic acid there was a dose- and time-dependent decrease in cell numbers. MCF-7 cells were more resistant than DU-145 cells (half maximal inhibitory concentrations of 122 and 90 microM, respectively). Ibandronic acid induced apoptosis in both cell lines. The study showed an apoptosis-mediated cytotoxic effect for ibandronic acid (in addition to the already known osteoclast inhibiting effect) in breast cancer patients with bone metastases; which was also observed in prostate cancer cells. Further clinical studies involving breast and prostate cancer patients with bone metastases are warranted to confirm these findings.

Topics: Apoptosis; Blotting, Western; Bone Density Conservation Agents; Bone Neoplasms; Bone Resorption; Breast Neoplasms; Caspase 3; Caspase 7; Cell Proliferation; Diphosphonates; Drug Resistance, Neoplasm; Female; Humans; Ibandronic Acid; Male; Neoplasms, Hormone-Dependent; Prostatic Neoplasms; Tumor Cells, Cultured

PubMed: 21309480
DOI: 10.1177/147323001003800511

Review

Authors: Jean-Yves Reginster, Olivier Malaise, Audrey Neuprez...

Bisphosphonates are the most widely prescribed drugs in osteoporosis today. They have unequivocally shown their ability to reduce fracture rate at the spine (alendronic acid, risedronic acid, ibandronic acid) and at the hip (alendronic acid and risedronic acid). However, their dosage and administration procedures and the adverse reactions induced by their oral intake are responsible for low adherence. Therefore, intermittent regimens have been developed. Weekly alendronic acid and risedronic acid provide similar benefits, in terms of bone mineral density (BMD) and changes in biochemical markers, as those seen with their daily formulations. Ibandronic acid has been shown to reduce vertebral fractures when given intermittently. Ibandronic acid given orally monthly and intravenously every 2 or 3 months provides increases in BMD similar to the daily formulation. Yearly intravenous infusions of zoledronic acid are currently being evaluated for their ability to reduce fractures. If the efficacy and safety of bisphosphonates given at administration intervals longer than weekly are confirmed, this might significantly improve patient adherence and long-term outcomes of bisphosphonate treatment in postmenopausal osteoporosis.

Topics: Aged; Bone Density; Bone Density Conservation Agents; Diphosphonates; Drug Administration Schedule; Female; Humans; Osteoporosis, Postmenopausal; Treatment Outcome

PubMed: 17503893
DOI: 10.2165/00002512-200724050-00001

Authors: Ioannis Fotopoulos, Vasileios Zisis, Theodoros Lillis...

BACKGROUND

The aim of this case report is to present an interesting case of bisphosphonate-related osteonecrosis of the jaw, involving the maxilla and the maxillary sinus, as a result of per os administration of ibandronic acid.

METHODS

A female patient, 62 years old, was referred to the Department of Dentoalveolar Surgery, Surgical Implantology and Radiology, School of Dentistry, Aristotle University of Thessaloniki, Greece, complaining about pain in the first quadrant. Her medical history revealed per os bisphosphonate administration for the past four years. Subsequently, the cone-beam computed tomography examination revealed a small sequestrum of bone, surrounded by radiolucency, in proximity with the sinus floor. The clinical examination didn't reveal any pathological clinical signs.

RESULTS

Based on the radiological examination, a surgical approach was implemented to remove the necrotic bone, irrigate the alveolar process and the sinus with saline, and finally achieve primary closure, after which, the patient healed uneventfully. The osteonecrosis was attributed to the bisphosphonate administration.

CONCLUSIONS

Bisphosphonate-related osteonecrosis of the jaw without obvious or with minor implication of gingival tissues is a diagnostic challenge indicating an early stage of this adverse reaction. Imaging is critical for the early detection of those cases. After careful choice of the case the proper surgical intervention could be effective to eliminate a future advancement of bone destruction. The prevention of osteonecrosis of the jaw can be achieved through the provision of adequate education to dental medicine practitioners, medical doctors, and patients.

PubMed: 38222881
DOI: 10.5037/jomr.2023.14405

Authors: T Frank, I Dewenter, S Otto...

BACKGROUND

Quality of life research with respect to patient reported outcomes (PROs) other than pain has not yet been conducted in the field of Diffuse Sclerosing Osteomyelitis. This cross-sectional study aims to investigate changes in quality of life regarding 34 subjective parameters in patients with diffuse sclerosing osteomyelitis after intravenous Ibandronic acid administration (6mg).

MATERIAL AND METHODS

15 patients (11 female, 4 male) with diffuse sclerosing osteomyelitis (DSO) treated with 6mg of Ibandronic acid completed the standardized questionnaires (EORTC QLQ-C30, EORTC QLQ-H&N35, OHIP-G 14) considering quality of life before and two weeks after infusion.

RESULTS

All 15 patients reported a significantly improved quality of life after administration of Ibandronate. Patients reported improvements in oral health associated quality of life as well as reduction of pain and intake of analgesics. In addition patients reported a significant improvement in fatigue, sexuality, social interactions, emotional, cognitive and role functioning. Furthermore patients reported an improvement in mouth opening, weight loss and loss of appetite as well as a reduction of speech and swallowing problems. Moreover, insomnia occurred less frequently after bisphosphonate infusions.

CONCLUSIONS

The study evaluates patients subjectively benefit from a standardized Ibandronic acid regimen. A significantly improved quality of life after administration of Ibandronate was observed in all 15 patients.

Topics: Humans; Female; Male; Quality of Life; Cross-Sectional Studies; Ibandronic Acid; Middle Aged; Aged; Osteomyelitis; Bone Density Conservation Agents; Infusions, Intravenous; Jaw Diseases; Adult; Diphosphonates

PubMed: 39396148
DOI: 10.4317/medoral.26761

Randomized Controlled Trial

Bioequivalence study of two formulations of ibandronic acid 150-mg film-coated tablets in healthy volunteers under fasting conditions: a randomized, open-label, three-way, reference-replicated crossover study.

Authors: Augusto Filipe, Pedro Pedroso, Susana Almeida...

AIMS

This bioequivalence study aimed to compare rate and extent of absorption of a generic medicinal product of ibandronic acid 150-mg film-coated tablet versus Bonviva(®).

METHODS

This was a single-centre, open-label, randomized, three-way, three-sequence, reference-replicated, crossover bioequivalence study, under fasting conditions. A single oral dose of ibandronic acid as one 150-mg film-coated tablet was administered in each study period. Each washout period lasted 14 days. Blood samples were collected according to a predefined sampling schedule and up to 48.0 hours after administraton in each period. Plasma concentrations of ibandronic acid were measured using a liquid chromatograph-mass spectrometry/mass spectrometry method. Bioequivalence between generic and reference medicinal products is acceptable if the 90 % confidence intervals (CI) of ratio of least-squares means between the test and the reference product of ln-transformed area under the serum concentration-time curve from time zero to time of last measurable concentration (AUC0-t ) is within the 80.00-125.00 % interval. Prospectively, a scaled average bioequivalence approach for maximum serum concentration (C max) was established.

RESULTS

153 healthy volunteers were enrolled and randomized. After the test formulation (T) and first and second Bonviva(®) (R) dosing, the C max was 96.71 ± 90.19 ng/mL, 92.67 ± 91.48 ng/mL and 87.94 ± 60.20 ng/mL and the AUC0-t was 390.83 ± 287.27 ng·h/mL, 388.54 ± 356.76 ng·h/mL and 383.53 ± 246.72, respectively. Ratios of T/R and 90 % CI were 100.92 % (94.35-107.94) for AUC0-t , 100.90 % (94.37-107.88) for AUC0-inf and 102.56 % (95.05-110.67) for C max.

CONCLUSIONS

Test formulation of ibandronic acid is bioequivalent in rate and extent of absorption to Bonviva(®) following a 150-mg dose, under fasting conditions.

Topics: Absorption, Physiological; Administration, Oral; Adolescent; Adult; Aged; Chemistry, Pharmaceutical; Cross-Over Studies; Diphosphonates; Dose-Response Relationship, Drug; Fasting; Female; Healthy Volunteers; Humans; Ibandronic Acid; Male; Middle Aged; Tablets; Therapeutic Equivalency; Young Adult

PubMed: 24756462
DOI: 10.1007/s40268-014-0044-x

Authors: Jiping Shen, Zheng Ke, Shuangshuang Dong...

BACKGROUND Numerous randomized controlled trials (RCTs) have evaluated pharmacological therapies for osteoporosis. The aim of this Bayesian network meta-analysis was to compare the efficacy and safety of pharmacological therapies for osteoporosis patients. MATERIAL AND METHODS The electronic databases of PubMed, Embase, and Cochrane Library were systematically searched for eligible RCTs from their inception up to January 2021. The primary endpoints were all fractures, vertebral fractures, and non-vertebral fractures, while the secondary endpoints were fractures at hip or peripheral locations, bone mineral density (BMD) at various sites, and potential adverse events. RESULTS We included 79 RCTs reporting a total of 108 797 individuals in the final quantitative analysis. The results of network analysis indicated that romosozumab (92.1%) was the most effective in reducing the risk for all fractures, with the best therapeutic effects on vertebral fracture (97.2%) and non-vertebral fracture (88.0%). Romosozumab (92.5%) provided better therapeutic effects for the reduction of hip fracture. The best treatment agents for improving whole-body BMD (100.0%), spine BMD (95.7%), hip BMD (92.4%), femoral neck BMD (86.7%), and trochanter BMD (95.5%) were alendronate, strontium ranelate, ibandronate, risedronate, and ibandronate, respectively. Finally, the use of bazedoxifene was associated with the highest incidence of any upper-gastrointestinal event, nasopharyngitis, and back pain, while risedronate was associated with higher incidence of abdominal pain and dyspepsia. CONCLUSIONS This study found that romosozumab yielded the best effects for preventing fracture risk, while abaloparatide was the most effective in reducing the risk of vertebral fracture and non-vertebral fracture.

Topics: Bone Density; Bone Density Conservation Agents; Female; Hip Fractures; Humans; Ibandronic Acid; Osteoporosis; Osteoporosis, Postmenopausal; Risedronic Acid; Spinal Fractures

PubMed: 35430576
DOI: 10.12659/MSM.935491