Bisphosphonates In Patients Research Articles

Effect of zoledronic acid and pamidronate on renal function.

There is limited data on the effect bisphosphonates have on renal function and the use of bisphosphonates in patients with baseline renal dysfunction. The purpose of this study was to determine the incidence of acute kidney injury (AKI) in patients after receiving zoledronic acid or pamidronate. A retrospective cohort analysis was conducted of patients who received one dose of a bisphosphonate, either zoledronic acid or pamidronate. The primary objective of this study was to determine the incidence of AKI after bisphosphonate administration. Baseline characteristics were compared, and unadjusted analyses of primary and secondary outcomes were completed using Pearson's chi-square or Fisher's exact test for categorical data and Mann-Whitney U test for continuous data. There was no difference found in AKI incidence between zoledronic acid and pamidronate (17.1% vs. 15.0%; p = 1.00). Additionally, there was no difference found in AKI incidence between patients with baseline renal dysfunction and those without, (25.0% vs. 15.0%; p = 0.322). There were no differences observed in either corrected calcium within seven days or serum creatinine (SCr) within 30 days returning to baseline after administration, nor were there differences in fever or hypophosphatemia incidences. Bisphosphonates may be used to treat hypercalcemia of malignancy in patients with and without renal dysfunction. AKI may occur post infusion; however, long-term effects on renal function are infrequent when hydrating patients prior to administration and adhering to the manufacturer's recommended infusion rate.

Real world clinical outcomes when discontinuing denosumab or bisphosphonates in patients with surgically managed osteoporotic vertebral compression fractures: a population-based cohort study

BACKGROUND CONTEXTOsteoporotic vertebral compression fractures (OVCFs) are common fragility fractures. Patients who undergo surgical treatment for their initial OVCFs warrant particular attention because there is an elevated risk of subsequent vertebral fractures and other types of fragility fractures. However, the optimal osteoporosis treatment for this specific patient group is less investigated. PURPOSEThis study compares the risk of subsequent osteoporotic fractures and mortality rate for patients who are initiated with denosumab and bisphosphonates and determines the effect of adherence to treatment. STUDY DESIGNRetrospective nationwide cohort study PATIENT SAMPLEA total of 2,858 patients who had surgically-managed osteoporotic vertebral compression fractures. OUTCOME MEASURESThe risk of osteoporotic fractures, vertebral fractures, nonvertebral fractures and death. METHODSThis is a retrospective nationwide cohort study that uses the National Health Insurance Research Database. Patients aged ≥50 years who were admitted for surgical interventions for OVCF between 2012 and 2016 and subsequently received denosumab or bisphosphonates for one year were included. Patients were stratified according to their antiosteoporosis medications and adherence to treatment. A multivariable, time-varying Cox proportional hazards model was used to determine the risk of osteoporotic fractures, vertebral fractures, nonvertebral fractures and death. RESULTSA total of 2,858 patients were included in this study: 1,123 patients in the denosumab group and 1,735 patients in the bisphosphonates group. Compared to persistent denosumab users, the nonpersistent denosumab users, persistent bisphosphonate users and nonpersistent bisphosphonate users had a greater risk of osteoporotic fractures, with respective hazard ratios of 1.64 (95% confidence interval [CI], 1.16–2.32), 1.74 (95% CI, 1.25–2.42) and 1.53 (95% CI, 1.14–2.06). If osteoporotic fractures were divided into nonvertebral and vertebral fractures, none of the groups exhibited an increased risk of vertebral fractures compared to persistent denosumab users, with an HR of 1.00 (95% CI: 0.54–1.88) for nonpersistent denosumab users, 1.64 (95% CI: 0.96–2.81) for persistent bisphosphonate users and 1.52 (95% CI: 0.95–2.43) for nonpersistent bisphosphonate users. However, there was a significantly greater risk of nonvertebral fracture, with respective hazard ratios of 2.04 (95% CI, 1.33–3.11), 1.80 (95% CI, 1.18–2.76) and 1.56 (95% CI, 1.06–2.27) for nonpersistent denosumab users, persistent bisphosphonate users and nonpersistent users. Noteworthy, nonpersistent denosumab users exhibited a significantly greater risk of mortality than persistent denosumab users, with a hazard ratio of 3.12 (95% CI, 2.22–4.38). CONCLUSIONSIn terms of patients with OVCFs who require hospitalization and surgical intervention, those who receive ongoing denosumab treatment exhibit less risk of developing subsequent osteoporotic fractures than those who receive bisphosphonates or nonpersistent denosumab treatment. However, discontinuation of denosumab is associated with a significantly increased risk of subsequent fractures and mortality. Therefore, adherence to the treatment is crucial for patients who are initiated with denosumab.

Clinical Efficacy of Bisphosphonates in Treating Osteoporosis in Diabetes Patients: A Meta-Analysis.

The aim of the study was to explore the clinical efficacy of bisphosphonates in patients with osteoporosis in diabetes patients by meta-analysis. Six databases were systematically searched from inception to January 30,2023. Studies evaluating the treatment of diabetic osteoporosis with bisphosphonates were included. Key outcome measures, such as bone mineral density (BMD), bone metabolism markers, pain improvement, and safety assessments, were extracted and analyzed. STATA MP V17.0 was used to calculate the combined effect size. After searching Chinese and English databases, 15 studies met the inclusion criteria of this study. The results of the meta-analysis showed that the BMD of patients with osteoporosis in diabetes increased significantly after bisphosphonate treatment, and the lumbar BMD increased by 0.08 g/cm² (95% CI: 0.05-0.11). Femoral neck BMD increased by 0.06 g/cm² (95% CI: 0.01-0.11); Ward's triangle BMD increased 0.07 g/cm² (95% CI: 0.04-0.09); and trochanter BMD increased by 0.06 g/cm² (95% CI: 0.04-0.08). In addition, bone alkaline phosphatase increased 1.95 μg/l (95% CI: 1.18-2.72), while serum tartrate-resistant acid phosphatase-5b decreased 1.28 U/l (95% CI: -1.81-0.75). Moreover, improvements in pain were statistically significant. The effects of bisphosphonates on osteocalcin (MD: -0.07; 95% CI: -1.12-1.25), serum calcium (MD: 0.01; 95% CI: -0.03-0.04), serum phosphorus (MD: 0.04; 95% CI: -0.03-0.10) and medication safety (OR: 1.75; 95% CI: 1.29-2.37) were not statistically significant. Bisphosphonates have a significant positive effect on bone mineral density and bone metabolism in patients with osteoporosis in diabetes and have good safety.

Evaluating calcium channel blockers and bisphosphonates as otoprotective agents in cochlear implantation hearing preservation candidates

Objectives Evaluate potential effects of calcium channel blockers (CCB) and bisphosphonates (BP) on residual hearing following cochlear implantation. Methods Medications of 303 adult hearing preservation (HP) candidates (low frequency pure tone average [LFPTA] of 125, 250, and 500 Hz ≤80 dB HL) were reviewed. Postimplantation LFPTA of patients taking CCBs and BPs were compared to controls matched by age and preimplantation LFPTA. Results Twenty-six HP candidates were taking a CCB (N = 14) or bisphosphonate (N = 12) at implantation. Median follow-up was 1.37 years (range 0.22–4.64y). Among subjects with initial HP, 29% (N = 2 of 7) CCB users compared to 50% (N = 2 of 4) controls subsequently lost residual hearing 3–6 months later (OR = 0.40, 95% CI = 0.04–4.32, p = 0.58). None of the four BP patients with initial HP experienced delayed loss compared to 50% (N = 2 of 4) controls with initial HP (OR = 0.00, 95% CI = 0.00–1.95, P = 0.43). Two CCB and one BP patients improved to a LFPTA <80 dB HL following initial unaided thresholds that suggested loss of residual hearing. Discussion There were no significant differences in the odds of delayed loss of residual hearing with CCBs or BPs. Conclusion Further investigation into potential otoprotective adjuvants for maintaining residual hearing following initial successful hearing preservation is warranted, with larger cohorts and additional CCB/BP agents.

Management of Vertebral Fragility Fracture in Older People: Recommendations from a Spanish Consensus of Experts.

Vertebral fragility fractures (VFF) pose a challenge for appropriate care. The aim of this study was to develop consensus recommendations for the management of VFF in older people from a multidisciplinary approach. Specialists in osteoporosis belonging to different scientific societies reviewed the main clinical practice guidelines published in Spain in 2014. Thirty-five recommendations for the management of VFF were evaluated by seven experts using an anonymous survey. Consensus was defined as 80% of responses of 8 (agree) and 9 (strongly agree) on a Likert scale. Consensus was achieved in 22 recommendations (62.8%). The experts agreed on the need for anamnesis, clinical assessment, and laboratory tests, including erythrocyte sedimentation rate, proteinography, and the assessment of levels of calcium, vitamin D, alkaline phosphatase, and thyroid-stimulating hormone. Optional tests, such as bone turnover markers (BTMs), magnetic resonance imaging, bone scintigraphy, or using a fracture risk assessment tool (FRAX®), did not achieve an agreed consensus. Also, there was consensus regarding the administration of calcium/vitamin D supplements, the withdrawal of toxic habits, and personalized physical exercise. Participants agreed on the administration of teriparatide for 24 months and then a switch to denosumab or bisphosphonates in patients at high risk of fracture. Specialists in osteoporosis, primary care physicians, and geriatricians should be involved in the follow-up of patients with VFF. Although there was multidisciplinary agreement on diagnostic tests and non-pharmacological and pharmacological treatment in frail older people, therapeutic objectives should be individualized for every patient. In addition to the specific recommendations, close collaboration between the geriatrician and the primary care physician is essential for the optimal chronic management of frail patients with fragility fractures.

Evaluating Route of Administration for Bisphosphonates in Patients with Metastatic Breast Cancer to the Bone: A Literature Review

Introduction: Metastatic bone disease, the condition where tumor cells spread from their origin tissue to bone, is common for breast and prostate cancer. Two main hypotheses, referred to as Paget’s “seed and soil” theory and Ewing’s anatomical theory, describe the homing of cancer cells to the bone. When breast cancer becomes metastatic and the tumor spreads to the bone, skeletal-related events can occur. Many patients use bone-modifying agents such as bisphosphonates (BPs) to manage skeletal deterioration. Given the longstanding history of BPs, this review aims to evaluate the efficacy and side effects of oral versus intravenous BPs as adjuvant treatment options for patients with metastatic breast cancer. Methods: Relevant literature was sourced through a search of the PubMed and Google Scholar databases, using established inclusion criteria for screening papers published between 1889 and the present. Results: Currently, there are three generations of BPs. Literature on the different generations reports that studies mainly use first-generation BPs for Paget’s disease and there is no significant effect of first-generation BPs on breast cancer survival rate. Second-generation BPs showed effectiveness in prolonging the progression of bone metastasis and decreasing distant recurrences to the bone in breast cancer patients. In attempts to improve the health outcomes of BPs, researchers examined third-generation BPs and found that they decreased skeletal-related events and pain levels. Discussion: Comparing oral to intravenous administration of BPs, both had overall similar effects in reducing skeletal complications; however, the side effects resulting from BP use vary depending on the route of administration. Patients administered intravenous BPs exhibit an acute phase response and renal complications, while oral BPs cause disruptions in the gastrointestinal tract. Cost-effectiveness varied by study depending on assumptions made in the analytic models. Conclusion: This novel review investigates the development of each generation of BPs to compare the implications of oral and intravenous administration. By accounting for differences across the three generations, healthcare providers can make informed decisions about BPs and create treatment plans tailored to the individual patient. Future research may explore how preexisting risk factors contribute to the occurrence of adverse effects of BP use.

Bisphosphonates and Dental Implants: A Systematic Review and Meta-Analysis.

The purpose of the present systematic review was to investigate the influence of bisphosphonates (BPs) on the dental implant failure rate and marginal bone loss (MBL). An electronic search was undertaken in three databases, plus a manual search of journals. Meta-analyses were performed, besides a meta-regression in order to verify how the log odds ratio (OR) was associated with follow-up time. The five- and ten-year estimated implant survivals were calculated. The review included 33 publications. Altogether, there were 1727 and 21,986 implants placed in patients taking and not taking BPs, respectively. A pairwise meta-analysis (26 studies) showed that implants in BP patients had a higher failure risk in comparison to non-BP patients (OR 1.653, p = 0.047). There was an estimated decrease of 0.004 in log OR for every additional month of follow-up, although it was not significant (p = 0.259). The global estimated implant survival in patients taking BPs after 5 and 10 years was 94.2% (95% CI, 94.0-94.4) and 90.1% (95% CI, 89.8-90.3), respectively. It was not possible to make any reliable analysis concerning MBL, as only two studies reported MBL results separated by groups. There is a 65.3% higher risk of implant failure in patients taking BPs in comparison to patients not taking this class of drugs.

Zoledronate and osteonecrosis of the jaw in osteoporosis: incidence and risk factors. Analysis of the French Pharmacovigilance Database

IntroductionBisphosphonate-related osteonecrosis of the jaw (BRONJ) have been characterized with the use of oral bisphosphonates in osteoporosis and zoledronate in oncology. Uncertainties remain, though, with the occurrence of BRONJ related to the use of zoledronate in osteoporosis. ObjectivesWe aimed to estimate the incidence and characterize the risk factors of zoledronate-associated BRONJ in osteoporosis as compared with oral bisphosphonates in real life setting. MethodsCases of BRONJ associated with zoledronate, alendronate or risedronate were extracted from the French pharmacovigilance database up to 2020. The incidence of BRONJ was estimated as their respective numbers related to cases of BRONJ in patients treated with bisphosphonates for osteoporosis, over the same period, according to the Medic’AM database. ResultsBetween 2011 and 2020, BRONJ incidence with zoledronate was 9.6/100,000 patient-year (PY), significantly higher than with alendronate (5.1/100,000 PY, P<0.001), and risedronate (2.0/100,000 PY, P<0.001). The number of patients treated with bisphosphonates has steadily decreased by 44.5% over 10 years. Meanwhile, the incidence of BRONJ decreased (5.8/100,000 PY in 2011; 1.5/100,000 in 2020), although a rebound was observed in 2018, including 47.6% of BRONJ following denosumab. Apart from classical risk factors, recent dental cares stood out in more than 40% of BRONJ, and zoledronate had a shorter exposure time than oral bisphosphonates. ConclusionsIn a real-life setting, our data confirm that zoledronate-associated BRONJ in osteoporosis is scarce, seeming slightly more common compared with oral bisphosphonates. We also raise awareness of dental care guidelines and greater vigilance when using bisphosphonates in patients with previous exposure to denosumab.

Retracted: Analysis of the Mechanism and Safety of Bisphosphonates in Patients with Lung Cancer and Bone Metastases.

[This retracts the article DOI: 10.1155/2021/5343104.].

Randomized controlled trial of daily teriparatide, weekly high-dose teriparatide, or bisphosphonate in patients with postmenopausal osteoporosis: The TERABIT study.

The effects of daily teriparatide (20μg) (D-PTH), weekly high-dose teriparatide (56.5μg) (W-PTH), or bisphosphonates (BPs) on areal bone mineral density (aBMD), bone turnover markers (BTMs), volumetric BMD (vBMD), microarchitecture, and estimated strength were investigated in postmenopausal osteoporosis patients. The study participants were 131 women with a history of fragility fractures. They were randomized to receive D-PTH, W-PTH, or BPs (alendronate or risedronate) for 18months. Dual-energy X-ray absorptiometry (DXA), BTMs, and high-resolution peripheral quantitative CT (HR-pQCT) parameters were evaluated at baseline and after 6 and 18months of treatment. The primary endpoint was the change (%) in cortical thickness (Ct.Th) after 18months' treatment compared with baseline. DXA showed that D-PTH, W-PTH, and BPs increased lumbar spine aBMD (+12.0%, +8.5%, and +6.8%) and total hip aBMD (+3.0%, +2.1%, and +3.0%), but D-PTH and W-PTH decreased 1/3 radius aBMD (-4.1%, -3.0%, -1.4%) after 18months. On HR-pQCT, D-PTH increased trabecular vBMD (Tb.vBMD) at the distal radius and tibia after 18months (+6.4%, +3.7%) compared with the BPs group, decreased cortical volumetric tissue mineral density (Ct.vTMD) (-1.8%, -0.9%) compared with the other groups, increased Ct.Th (+1.3%, +3.9%), and increased failure load (FL) (+4.7%, +4.4%). W-PTH increased Tb.vBMD (+5.3%, +1.9%), maintained Ct.vTMD (-0.7%, +0.2%) compared with D-PTH, increased Ct.Th (+0.6%, +3.6%), and increased FL (+4.9%, +4.5%). The BPs increased Tb.vBMD only in the radius (+2.0%, +0.2%), maintained Ct.vTMD (-0.6%, +0.3%), increased Ct.Th (+0.5%, +3.4%), and increased FL (+3.9%, +2.8%). D-PTH and W-PTH comparably increased Ct.Th, the primary endpoint. D-PTH had a strong effect on trabecular bone. Although D-PTH decreased Ct.vTMD, it increased Ct.Th and total bone strength. W-PTH had a moderate effect on trabecular bone, maintained Ct.vTMD, and increased Ct.Th and total bone strength to the same extent as D-PTH.

Radiologic zebra line sign in a patient with Langerhans cell histiocytosis on bisphosphonate therapy.

A 3-year-old boy was diagnosed with multi-system Langerhans cell histiocytosis (LCH) with bone, skin, lung, lymph node, and bone marrow involvement at 8 months of age. He achieved non-active disease (NAD) after chemotherapy with prednisolone, vincristine, and cytarabine. However, the patient presented with bone lesion relapse. Despite re-initiation of vinblastine and prednisolone, his bone lesion progressed, prompting treatment with three cycles of cladribine. While it provided some improvement, he presented with bone lesion relapse soon after cladribine therapy. Due to the recurrence of the bone lesion, we administered bisphosphonate therapy using monthly zoledronic acid for 6 months in addition to conventional chemotherapy, which resolved his bone lesion. The patient achieved NAD for 1 year. While he did not present with bone pain, radiographs obtained during bisphosphonate therapy revealed a “dense metaphyseal band sign,” also known as “zebra line sign,” at the tibia and fibula (Figure 1A−D). Nevertheless, 2 years after initiation of bisphosphonate therapy, his growth remained steady (Figure 1E). LCH is characterized as both neoplastic and inflammatory disease. Osteoclasts are crucial in the pathogenesis of LCH, especially in lytic bone lesions. Previous reports revealed that bisphosphonate therapy, including pamidronate and zoledronate, was effective in patients with LCH. Bisphosphonates reduce the activity of osteoclasts by inhibiting their recruitment, thereby resulting in the uncoupling of bone remodeling. The zebra line sign refers to the line of cartilage calcification persisting from the metaphysis into the diaphysis [1, 2]. This radiologic finding reflects the administration of bisphosphonate [3]. Although the zebra line sign seems to be a normal reaction to bisphosphonate therapy, hematology-oncology specialists are not familiar with this finding. In addition, the long-term side effects (e.g., short stature and fracture) remain unknown. This study highlights the importance of long-term follow-up to evaluate the safety profile of bisphosphonates in patients with LCH. The authors declare no conflict of interest.

Efficacy and Safety of Eldecalcitol for Osteoporosis: A Meta-Analysis of Randomized Controlled Trials.

ObjectEldecalcitol (ED-71) is a vitamin D analog for the treatment of osteoporosis. However, inconsistent results have been reported in this regard. Hence, this meta-analysis of randomized controlled trials (RCTs) aimed to assess the efficacy and safety of ED-71 for osteoporosis.MethodsThe PubMed, Embase, and the Cochrane Library databases were systematically searched to identify potential trials from inception until April 2021. The investigated outcomes included bone mineral density and fractures at various sites, and potential adverse events. The pooled effect estimates were calculated using weighted mean difference (WMD) and relative risk (RR) with 95% confidence interval (CI) using the random-effects model.ResultsEight RCTs involving 2368 patients were selected for the final meta-analysis. The pooled results showed that ED-71 were associated with a higher level of femoral neck (FN) bone mineral density (BMD) (WMD: 0.92; 95% CI: 0.24–1.60; P = 0.008), while it had no significant effect on lumbar spine BMD (WMD: 1.09; 95% CI: –0.11 to 2.30; P = 0.076) and hip BMD (WMD: 1.12; 95% CI: –0.16 to 2.40; P = 0.088). Moreover, the use of ED-71 could protect against the risk of all osteoporotic fracture (RR: 0.70; 95% CI: 0.55–0.88; P = 0.003) and vertebral fracture (RR: 0.74; 95% CI: 0.55–0.98; P = 0.038), while it did not affect the risk of nonvertebral fracture (RR: 0.53; 95%CI: 0.23–1.23; P = 0.140). The subgroup analyses found that the effects of ED-71 were superior to those of alfacalcidol on both BMD and fracture results. Moreover, the use of ED-71 plus bisphosphonate was associated with a greater improvement in BMD at various sites compared with bisphosphonate alone. Finally, ED-71 was associated with an increased risk of increased urine calcium level (RR: 1.69; 95% CI: 1.33–2.15; P < 0.001).ConclusionThis study found that the use of ED-71 could improve BMD and fractures at various sites, especially compared with alfacalcidol or a combination with bisphosphonate for patients with osteoporosis.Systematic Review Registration[http://www.crd.york.ac.uk/prospero], identifier [CRD42021270536].

Comparative Treatment Persistence with Bone-Targeting Agents Among Asian Patients with Bone Metastases from Solid Tumors: A Multinational Retrospective Cohort Study.

The efficacy of bone-targeting agents has been confirmed, but the generalizabilityof results to Asia is in question. We aimed to evaluate and compare treatment persistence and re-initiation with different bone-targeting agents among patients with bone metastases from solid tumors. This population-based cohort study included patients with bone metastasis with breast, lung, or prostate cancer who initiated bone-targeting agents, including denosumab, zoledronic acid, and pamidronate in Taiwan (2013-17), Hong Kong (2013-17), and Korea (2012-16). We described the patients' persistence with bone-targeting agents, by evaluating the interruption probability, and compared risks of treatment interruption. The rates of re-initiation with index bone-targeting agents were evaluated. We included 5127 patients (denosumab: 3440, zoledronic acid: 1210, pamidronate: 477) from Taiwan, 883 patients (denosumab: 458, zoledronic acid: 357, pamidronate: 68) from Hong Kong, and 4800 patients (zoledronic acid: 4068, pamidronate: 732) from Korea. Compared with zoledronic acid, denosumab had a lower risk of interruption in Taiwan (adjusted hazard ratio: 0.44; 95% confidence interval 0.40-0.48) and Hong Kong (0.36; 0.28-0.45). However, pamidronate was more likely to be interrupted than zoledronic acid in Taiwan (1.31; 1.11-1.54) and Korea (2.06; 1.83-2.32), but not in Hong Kong (1.13; 0.71-1.78). After discontinuation, original treatments with denosumab in Taiwan and zoledronic acid in Hong Kong were more likely to be resumed, while in Korea, the rates were similar among the bisphosphonates. Denosumab was associated with a lower risk of interruption than bisphosphonates in patients with bone metastases in Taiwan and Hong Kong. Further investigations may be required to verify patients' actual reasons for discontinuation.

Real-life short-term effectiveness of anti-osteoporotic treatments: a longitudinal cohort study

Introduction:Randomized clinical trials have shown that anti-osteoporotic treatments can increase bone mineral density (BMD) and reduce the incidence of fragility fractures. However, data on the real-life effectiveness of anti-osteoporotic medications are still scarce.Methods:We conducted a cohort study on women at high risk of fracture. We retrieved clinical and densitometric data from the DeFRA database, which derives from the DeFRA tool, a web-based fracture risk assessment tool. Multivariable Cox regression survival models were employed to analyze the effectiveness of different anti-osteoporotic drugs on fracture. In sensitivity analyses, we conducted 1:1 propensity score matching analyses.Results:Data on 50,862 women were available. Among these, 3574 individuals had at least two consecutive visits. The crude fracture rate was 91.9/1000 person-year for non-treated patients. The crude fracture rate in bisphosphonate users was 72.1/1000 person-year, in denosumab users was 58.2/1000 person-year, and in teriparatide users was 19.3/1000 person-year. Overall, we found that bisphosphonate use was associated with a 30% lower risk of fracture compared to no treatment [adjusted hazard ratio (aHR): 0.70, 95% confidence interval (CI): 0.50–0.98]. Treatment with denosumab and teriparatide were associated with 60% and 90% lower risk of fracture, respectively (aHR: 0.43, 95% CI: 0.24–0.75 and aHR: 0.09, 95% CI: 0.01–0.70). Bisphosphonate use was associated with a lower risk of fracture only after 1 year of treatment.Conclusion:In conclusion, we found that all anti-osteoporotic medications considered in the study effectively reduced the risk of fracture in the real-life. The effect of bisphosphonate on fracture risk was apparent only after the first year of treatment. Our findings do not support the use of bisphosphonates in patients at imminent risk of fracture.

Analysis of the Mechanism and Safety of Bisphosphonates in Patients with Lung Cancer and Bone Metastases.

Objective To explore the mechanism and safety of bisphosphonates in patients with lung cancer and bone metastases. Method A total of 104 patients with lung cancer and bone metastases in our hospital were selected and randomly divided into two groups: control group (n = 54) and research group (n = 50). Chemotherapy was given to the control group, and the research group was treated with bisphosphonate drugs. The quality of life, HAMA, HAMD score, VAS score, treatment effect, serum calcium and KPS score, inflammatory factor levels, and immune function were compared between the two groups. Result The quality of life in both groups was significantly increased (P < 0.05). The HAMA and HAMD scores of the research group decreased significantly than those of the control group after treatment (P < 0.05). The VAS scores of the two groups were significantly reduced (P < 0.05). The effective rates of treatment in the control group and the research group were 81.5% and 96.0%, respectively. Serum calcium was significantly decreased, and KPS score was significantly increased at weeks 1 and 6 after treatment, and the change was more obvious in the research group (P < 0.05). The levels of inflammatory factors in the two groups were significantly reduced, and the immune indicators were significantly increased. Conclusion Bisphosphonates have good effect on patients with lung cancer and bone metastases, which can improve anxiety and depression, reduce pain score, improve serum calcium level and immune function, and reduce inflammatory response. Therefore, bisphosphonate drug therapy is worth widely used.

Does Bisphosphonate Increase the Sclerosis of Tibial Subchondral Bone in the Progression of Knee Osteoarthritis-A Propensity Score Matching Cohort Study Based on Osteoarthritis Initiative.

Bisphosphonate has great potential in KOA therapy, but whether the anti-resorption mechanism of bisphosphonate aggravates sclerosis of subchondral bone remains unclear. We found that bisphosphonate use did not increase sclerosis of subchondral bone in established KOA, perhaps resolving some concerns about bisphosphonate in patients with KOA.Introduction: Most studies have focused on the protective effect of bisphosphonate on early knee osteoarthritis (KOA) through its anti-resorption mechanism in osteoclasts. However, late KOA has a decreased rate of resorption, which is the opposite of early KOA. The risk of subchondral bone sclerosis in late KOA after using bisphosphonate has not been investigated using morphometry.Methods: Forty-five patients who had ever used bisphosphonate (or 33 patients with current use) were matched with controls through propensity matching methods, including age, body mass index (BMI), sex, health status (12-Item Short Form Survey physical health score), physical activity level (Physical Activity Scale for the Elderly score), vitamin D use, and calcium use. At the baseline and 12-month (or 18-month) follow-up, bone mineral density (BMD) of the tibia and hip was measured by dual-energy X-ray absorptiometry (DXA), and medial tibial subchondral bone morphometry: bone volume fraction (BV/TV), trabecular thickness (Tb.Th), trabecular number (Tb.N), and trabecular separation (Tb.Sp) were calculated based on 3-T trabecular MRI. Data were obtained from the Bone Ancillary Study in the Osteoarthritis Initiative (OAI) project.Results: The yearly percentage change in hip BMD of the current bisphosphonate-use group was significantly greater than that of the non-bisphosphonate-use group (0.7% vs. −1%, P = 0.02). The other outcomes (BV/TV, Tb.N, Tb.Sp, Tb.Th, tibia medial BMD, and tibia lateral BMD) between the two groups presented no significant difference. The non-bisphosphonate-use group experienced a significant increase in Tb.Th [2%, 95% CI = (1%, 4%), P = 0.01], while the bisphosphonate-use group presented no significant change [1%, 95% CI = (−2%, 4%), P = 0.54].Conclusions: Bisphosphonate use did not increase sclerosis of subchondral bone in established KOA. Bisphosphonate might have a stage-dependent effect on subchondral bone in KOA initiation and progression.

O14 An atypical femoral fracture without a history of bisphosphonate use

Case report - IntroductionA 60-year-old female presented with an insufficiency fracture of the midshaft of the left femur and a persistently low serum alkaline phosphatase. A diagnosis of adult hypophosphatasia was made. We present this case alongside a series of other cases that we have identified locally and discuss the importance of identifying this condition in clinical practice.Case report - Case descriptionA 60-year-old female presented with left thigh pain and an 8-year history of polyarthralgia involving the medium-large sized joints. She had a traumatic fracture of the humerus 4 years previously. She had no history or examination findings suggestive of an inflammatory arthritis, connective tissue disease or systemic illness.An X-ray of left femur revealed a cortical-based lucency at the lateral cortex of midshaft. An MRI identified a focal area of cortical thickening but no evidence of bone marrow oedema suggestive of an osteoid osteoma. Finally, a CT scan confirmed the diagnosis of a healed stress fracture. The patient had never received any form of bisphosphonate treatment, no previous history of a non-traumatic fracture and no history of dental problems.Laboratory evaluation revealed persistently low levels of serum alkaline phosphatase (∼23 IU/L) with a normal vitamin D and PTH level. Bone density scan showed a T-score of -1.1 at the femoral neck and -2.6 at the lumbar spine. Serum pyridoxal phosphate level was elevated at 457 nmol/L (35-100). A diagnosis of adult hypophosphatasia was suspected and genetic study for ALPL gene confirmed the diagnosis.The following table summarises a number of other cases of adult hypophosphatasia, which we have identified locally. CaseAge / GenderPresentationAlkaline phospha tase (IU/L)Pyridoxal phosphate (nmol/L)Notes1 (Index case)62 / FWidespread pain, Atypical femoral fracture23457Genetic study confirmed278 / FWidespread pain, Osteomalacia22201Genetic study confirmed356 / MSon of Case 2, Osteoporosis, Diabetes mellitus22 – 29awaited Bisphosphonate stoppedGenetic study awaited 440 / FRecurrent metatarsal fractures, Low BMD24NormalBisphosphonate stopped548 / FPremature loss of teeth, fatigue, Widespread pain, Diabetes mellitus, hyperlipidaemia13-23327Genetic study confirmed675 / FSeronegative polyarthritis21-26120Genetic study awaitedCase report - DiscussionHypophosphatasia (HPP) is a rare inherited metabolic disease caused by mutations in the alkaline phosphatase liver type (ALPL) gene, localized on the chromosome region 1p36.1–34, encoding the tissue-nonspecific isoenzyme of alkaline phosphatase (TNSALP). The disease is related to a decrease in both level and activity of alkaline phosphatase enzyme (ALP). The clinical expression is highly variable, ranging from lethal forms to mild forms diagnosed in adults. Fractures, chondrocalcinosis, calcific periarthritis, and chronic muscle and bone pain are key features for the diagnosis of HPP in adults. Teriparatide has been used for treatment in some case reports with inconsistent results. Antiresorptive drugs are contraindicated as they can worsen underlying osteomalacia.Case report - Key learning pointsCheck for persistent low serum alkaline phosphatase levels in adults presenting with fragility fractures, crystal-related arthropathies and nonspecific generalised aches.Avoid bisphosphonates in patients with low alkaline phosphatase.

Management of Early Case of Maxilla Osteonecrosis in Patient with Bone Metastases on Bisphosphonates Using Platelet-Rich Fibrin as Adjuvant: Case Report

Although it remains relatively rare, osteonecrosis of the mandible and/or maxilla induced by intravenous infusion of bisphosphonates in patients suffering from bone metastatic cancers is a serious complication that affects the oral and maxillofacial region, its repercussion can be heavy and impacts quite negatively the patient's quality of life, despite its management is uncertain and complicated, a rapid intervention with a conservative approach if it is possible strengthen with the use of platelet-rich fibrin (PRF) as adjuvant seems to be very effective, thus enhancing the bone healing, limiting current manifestations and prevent more serious and extended complications. In this case report, we present a good evolution of an early stage of maxillary osteonecrosis that appeared four weeks after dental extraction by a general practitioner in a 60-year-old female treated with IV Bisphosphonates, IV Herceptin and Arimidex for bone metastatic breast cancer using conservative treatment combined with the use of autologous platelet-rich fibrin.

Cardioprotective effects of alendronate bisphosphonate in patients with ischemic heart disease associated with type 2 diabetes mellitus and osteoporosis

Introduction. Diabetes mellitus, cardiovascular diseases and osteoporosis are linked by common pathophysiological mechanisms.Objective. To evaluate the effect of alendronate bisphosphonate on cardiovascular outcomes in comorbid patients with ischemic heart disease (CHD) associated with type 2 diabetes mellitus (type 2 diabetes) and osteoporosis during a two-year follow-up.Materials and methods. A total of 112 women with comorbid pathology including osteoporosis, coronary artery disease, and type 2 diabetes were examined. The patients' condition was assessed at baseline and prospectively for 24 months with a combined endpoint assessment, including: mortality, readmission for cardiovascular diseases, the development of myocardial infarction (MI), stroke, atrial fibrillation. Women were divided into groups: group 1 (n = 59) included patients who received basic therapy for IHD and type 2 diabetes, group 2 (n = 53) included patients who, in addition to basic therapy for coronary artery disease and diabetes Type 2 was prescribed alendronic acid preparation.Results and discussion. According to the results of two-year follow-up, the patients were divided into two subgroups: patients with a favorable (n = 61) and unfavorable course of coronary artery disease (n = 51). At the same time, during prospective observation, the following was assessed: the frequency of hospitalizations for cardiovascular diseases, the dynamics of the functional class (FC) of exertional angina, the development of MI, stroke, atrial fibrillation, and mortality. A significant association of alendronate therapy with a favorable course of ischemic heart disease (OR = 0.26; 95% CI = 0.18-0.57; p = 0.008), a decrease in the risk of MI (OR = 0.32; 95% CI = 0.11-0.87; p = 0.018) and worsening of FC of exertional angina (OR = 0.4; 95% CI = 0.17-0.91; p = 0.014).Conclusion. Long-term (24 months) use of alendronate is an effective and safe method for the treatment of associated cardiovascular pathology, represented by coronary artery disease, type 2 diabetes and osteoporosis in postmenopausal women, reducing the risk of MI, worsening of FC of exertional angina. These results suggest a more aggressive prescription of alendronate for osteoporotic patients at very high cardiovascular risk.

Adjuvant bisphosphonate use in patients with early stage breast cancer: a physician survey.

PurposeDespite the increasing use of adjuvant bone-modifying agents (BMAs) such as zoledronate and clodronate in the treatment of patients with early stage breast cancer (EBC), little is known about real world practice patterns. A physician survey was performed to address this deficit and determine interest in clinical trials of alternative strategies for BMA administration.MethodsCanadian oncologists treating patients with EBC were surveyed via an anonymized online survey. The survey collected information on: physician demographics, knowledge and interpretation of adjuvant bisphosphonate guidelines, and real world prescribing practices. Questions also determined thoughts around the design of future adjuvant BMA trials.ResultsOf 127 surveyed physicians, 53 eligible invitees responded (response rate 42%). The majority of physicians are offering high-risk postmenopausal patients adjuvant BMAs. The most common BMA regimen was adjuvant zoledronate (45/53, 85%) every 6 months for 3 years. Concerns around toxicities and repeated visits to the cancer centre were perceived as the greatest barriers to adjuvant bisphosphonate use. Respondents were interested in future trials of de-escalation of BMAs comparing a single infusion of zoledronate vs. 6-monthly zoledronate for 3 years. The most favoured primary endpoints for such a trial included disease recurrence and fragility fracture rates.ConclusionQuestions around optimal use of adjuvant bisphosphonates in patients with EBC still exist. There is interest among physicians in performing trials of de-escalation of these agents. The results of this survey will assist in designing pragmatic clinical trials to address this question.Supplementary InformationThe online version contains supplementary material available at 10.1007/s10549-021-06147-1.