Use Of Bisphosphonates Research Articles

The Effect of Preoperative Bisphosphonate Use on Total Hip Arthroplasty Outcomes

BackgroundPatients undergoing total hip arthroplasty (THA) commonly have osteoporosis for which bisphosphonates (BPs) are Food and Drug Administration (FDA)-approved for treatment. Bisphosphonate use post-THA is associated with decreased periprosthetic bone loss or revisions, and increased longevity of implants. However, evidence is lacking for preoperative bisphosphonate use in THA recipients. This study investigated the association between bisphosphonate use pre-THA and outcomes. MethodsA retrospective review of a national administrative claims database was conducted. Among THA recipients who had a prior diagnosis of hip osteoarthritis and osteoporosis/osteopenia, the treatment group (BP-exposed) consisted of patients who had a history of bisphosphonate use at least 1 year before THA; controls (BP-naive) comprised patients who did not have preoperative bisphosphonate use. The BP-exposed were matched to BP-naive in a 1:4 ratio by age, sex, and comorbidities. Logistic regressions were used to calculate the odds ratio for intraoperative and 1-year postoperative complications. ResultsThe BP-exposed group had significantly higher rates of intraoperative and 1-year postoperative periprosthetic fractures (odds ratio (OR): 1.39, 95% confidence interval (CI): 1.23, 1.57) and revisions (OR: 1.14, 95% CI: 1.04, 1.25) compared with the BP-naive controls. BP-exposed also experienced higher rates of aseptic loosening, dislocation, periprosthetic osteolysis, and stress fracture of the femur or hip/pelvis compared to the BP-naive controls, but these values were not statistically significant. ConclusionThe use of bisphosphonates in THA patients preoperatively is associated with higher rates of intraoperative and 1-year postoperative complications. These findings may impact the management of patients undergoing THA who have a prior diagnosis of osteoporosis/osteopenia and use of bisphosphonates. Level of evidenceRetrospective Cohort Study (Level 3).

Bisphosphonate use for glucocorticoid-induced osteoporosis in older patients with immune thrombocytopenia: a clinical perspective.

Prednisolone, used as a standard initial treatment for immune thrombocytopenia (ITP), is an important risk factor for osteoporosis. Recently, we found that prescription of bisphosphonate during initial loading of prednisolone may prevent reduction in bone mineral density and development of glucocorticoid-induced osteoporosis (GIO) in older patients with ITP receiving prolonged steroid therapy. In this review, I describe the treatment options for older patients with ITP, and present the best practices for screening, evaluating, and diagnosing ITP. I also summarize the literature from 2017 to 2022 on the treatment options for ITP, including discussions on the contraindications and side effects, with an emphasis on GIO, and the relative merits of bisphosphonates as a co-treatment for prevention of GIO. Finally, I present a perspective and an expert recommendation on how older patients with ITP would best be served in the future.

The feasibility of discriminating BRONJ lesion bone with Raman spectroscopy.

With the frequent use of Bisphosphonates (BPs), the morbidity of BP-related osteonecrosis of the jaw (BRONJ) is also increasing. However, the prevention and treatment of BRONJ is faced with enormous challenges. This study aimed to illuminate the influence of BP administration in the rat mandible and explore the feasibility of discriminating BRONJ lesion bone with Raman spectroscopy. First, we explored the time- and mode-dependent effects of BP administration on the rat mandible with Raman spectroscopy. Second, the BRONJ rat model was constructed, and the lesion and healthy bone components were analyzed using Raman spectroscopy. When only BPs were administered, no rats showed BRONJ symptoms, and no difference could be found in the Raman spectra. However, when combined with local surgery, six (6/8) rats showed BRONJ symptoms. The Raman spectra also showed a significant difference between the lesion and healthy bone. In the progression of BRONJ, BPs and local stimulation play an essential role. Both BPs administration and local stimulation need to be controlled to prevent BRONJ. Moreover, BRONJ lesion bone in rats could be discriminated with Raman spectroscopy. This novel method would become a complement in the treatment of BRONJ in the future.

Abstract #1408105: Treatment of Bisphosphonate Associated Atypical Femur Fracture with a Combination of Teriparatide and a Novel Surgical Technique

Atypical femur fractures (AFF) caused by long term Bisphosphonate use are associated with high rates of delayed healing and non-union, posing a significant challenge in the management of these patients. We describe the case of a 64-year-old female with osteopenia on Bisphosphonate therapy for 15 years who sustained a displaced left AFF following a fall from standing height. She reported a 6-month history of antecedent left groin pain. Radiographs of the left femur showed an acute displaced transverse diaphyseal fracture with lateral cortical thickening and beaking. The right femur radiograph showed features of abnormal cortical remodeling with thickened, irregular cortices. DEXA showed T-scores of -2.1 at the left femoral neck, -1.4 at the left total hip, and -1.4 at the lumbar spine. She underwent an open reduction and internal fixation with insertion of a cephalomedullary nail placed in compression mode. A novel technique of intraoperative removal of the endosteal hypertrophied cortical bone at the fracture with a Midas rex cutting burr was used and there was excellent cortical contact after reduction. She had immediate relief of her pain and was permitted to fully weight-bear postoperatively. Her bisphosphonate was stopped immediately and Teriparatide was initiated at 7 weeks post-operatively. Radiographs 8 weeks after initiation of Teriparatide showed evidence of normal fracture union with mature callus formation. AFF caused by prolonged Bisphosphonate use have a high rate of delayed healing and non-union due to abnormal bone remodeling. Use of Teriparatide post-operatively has been shown to reduce healing time in recent small studies in surgically treated patients. Our case demonstrates expedited healing time when Teriparatide was combined with a novel surgical technique involving removal of a portion of the abnormal fracture end and placement of an intramedullary nail in compression mode. Furthermore, the patient had radiographic evidence of cortical thickening on her right femur, increasing her risk for contralateral AFF. Prophylactic surgical stabilization was recommended but the patient has deferred this. She remains fracture-free and pain-free on the right side, suggesting a possible benefit of Teriparatide use in patients at risk for impending AFF. Our case demonstrates an expedited healing time (3.5 months) relative to previously reported average healing times for AFF (10.7 months), supporting the use of the combination of Teriparatide and a novel surgical technique.

2 Effects of extra-label bisphosphonate use on growth parameters and endocrine biomarkers of bone health in juvenile horses

Extra-label bisphosphonate use in juvenile horses is widespread despite limited scientific understanding of biological and welfare impacts on skeletally immature, exercising horses. The objective of this study was to determine the effects of bisphosphonate (clodronate disodium; CD) on endocrine regulation of bone growth, hypothesizing there would be no effect. To test this, 32 Quarter Horses were stratified by age (500 ± 13 d of age), BW (336 ± 26 kg), sex (n = 16 males, n = 16 females), and initial bone optical density by aluminum equivalence into 4 treatment groups for a 168-d trial. The experimental period was divided into 2 phases mimicking sales preparation (Phase I: d 0–83) and early performance training (Phase II: d 84–168). Horses were housed in individual stalls (3.6 m × 7.3 m) and fed diets formulated to meet nutrient requirements. Investigators were blinded, and all horses received iso-volumetric intramuscular injections of either 1.8 mg/kg BW CD (OSPHOS®) or saline (placebo) on d 0, 42, 84, and 126. Treatments consisted of control (CON; n = 8), single-dose CD (1X; n = 8; d 84), 2-dose CD (2X; n = 8; d 0, 84), and 4-dose CD groups (4X;n = 8; d 0, 42, 84, 126). Physical measurements including BW, wither height (WH), hip height (HH), body length (BL), and heart girth (HG) circumference were recorded every 42 d from d 0. Likewise, serum samples were collected every 42 d before treatment administration to quantify growth hormone (GH), calcitonin (CT), parathyroid hormone (PTH), and ionized calcium. Data were analyzed using PROC MIXED of SAS. All physical growth measurements increased over time (P ≤ 0.01) but were not affected by treatment (P ≥ 0.62). Similarly, there was no effect of treatment (P = 0.44) for GH, but concentrations tended to decrease over time as growth rate slowed (P = 0.09). A treatment ´ time interaction was observed for PTH (P = 0.05) where concentrations increased following 2 clodronate doses. Specifically, concentrations increased on d 84 in 4X and on d 126 in 2X following the second administration of clodronate while 1X and CON remained unchanged. There was no effect of treatment (P = 0.98), time (P = 0.33), nor treatment × time interaction (P = 0.61) for CT despite the increase in PTH. Ionized calcium concentrations decreased over time (P < 0.01) with no effect of treatment (P = 0.26) or treatment × time interaction (P = 0.32). These results suggest that while administration of bisphosphonate has no effect on growth morphometrics, its repetitive use alters PTH concentrations after 2 doses.

Abstract #1406447: A Case of Severe Hypercalcemia After Recovery from Rhabdomyolysis that was Refractory to Hemodialysis

Rhabdomyolysis (RBD) is severe skeletal muscle injury which often results in acute kidney injury (AKI) and significant electrolytes abnormalities. We herein describe a case of severe hypercalcemia that occurred during the recovery phase of RBD that was successfully treated with intravenous (IV) pamidronate. A 58-year-old male with history of cirrhosis, IgA nephropathy and chronic kidney disease presented with lower extremity weakness and was found to have AKI due to statin-induced RBD. Creatinine Kinase (CK) was > 30000 U/L [30-200], BUN 78 mg/dl [ 6-22], Creatinine 5.78 mg/dl [ 0.77-1.25], corrected Calcium (Ca) 7.0 mg/dl [8.6- 10.2], Ionized Ca 2.5 mg/dl [4.5- 5.3], Phosphorus 6.7 mg/dl [2.3-4.7], 25-OH Vitamin D 4.8 ng/ml [30 -80] and Parathyroid hormone (PTH) 333 ng/ml [8.7-77.1]. The patient received IV calcium gluconate, vitamin D supplementation and hemodialysis (HD) and was started on calcitriol 0.25 mg three times a week. He was discharged on calcitriol, calcium acetate and vitamin D with a corrected Ca of 9.1 mg/dl. One week later, the patient was readmitted with confusion and a corrected Ca of 15.3 mg/dl, phosphorus of 7 mg/dl, CK of 131 U/L, 25- OH vitamin D 10 ng/ml, PTH 11.4 ng/ml. Additional workup for hypercalcemia was unremarkable. His hypercalcemia persisted despite HD with low calcium baths, gentle IV hydration, and IV furosemide. Calcitonin 4 units/kg was initiated but his Ca remained 12.4mg/dl after 48 hours. IV pamidronate 30 mg was given and within 5 days, his Ca level was 9.4 mg/dl, reaching a nadir of 8.9 mg/dl. RBD is commonly associated with hypocalcemia in the acute phase. Hypercalcemia can also occur in the recovery phase, but few reports exist and the appropriate management has not been established. As in our case, overtreatment of hypocalcemia may exacerbate hypercalcemia. The pathophysiology of the hypercalcemia may be due to mobilization of Ca from injured muscles and soft tissue deposits. Secondary hyperparathyroidism can also contribute to a hypercalcemic response. Hypercalcemia due to RBD is usually self-limited but more severe cases can occur. Few have reported on the use of bisphosphonates for this condition. In our case, multiple treatments were not successful in lowering calcium. Despite concerns that bisphosphonates may not successfully lower calcium, since hypercalcemia was not mediated by bone turnover, calcium decreased after bisphosphonate therapy and no adverse effects were experienced. Therefore, bisphosphonate therapy can be considered in refractory post-rhabdomyolysis hypercalcemia.

A case of elevated P1NP levels: uncovering Paget's disease in a postmenopausal woman

INTRODUCTION: Procollagen type 1 N-terminal propeptide (P1NP) is a marker of bone formation that is frequently used in the diagnosis and management of osteoporosis. Elevated levels of P1NP may indicate increased bone turnover, which can be a sign of various bone disorders. Paget’s disease of bone is a chronic disorder characterized by excessive and disorganized bone remodeling. The exact cause of Paget’s disease is unknown, but it is thought to be related to genetic factors and viral infections.CASE REPORT: A 48-year-old postmenopausal woman presented with a six-month history of low back pain. Her DEXA scan showed osteopenia in the lumbar spine, and her serum P1NP level was markedly elevated. Further workup revealed a diagnosis of Paget’s disease of bone. The patient was treated with bisphosphonates, resulting in significant improvement in her symptoms and normalization of her P1NP level.CONCLUSIONS: This case highlights the importance of considering Paget’s disease as a potential cause of elevated P1NP levels. The use of bisphosphonates can be effective in treating Paget’s disease and improving bone health. Elevated P1NP levels can be seen in various bone disorders, and clinicians should be aware of its potential clinical implications. The measurement of P1NP is routinely included in the workup of patients with suspected bone disorders, and its levels are used to monitor response to treatment.

Metastasis prevention with bone-targeted agents: a complex interaction between the microenvironment and tumour biology.

The use of bone-targeted treatments has transformed the clinical care of many patients with metastatic breast cancer. In addition, due to the profound effects of bisphosphonates and denosumab on bone physiology and the bone microenvironment, the potential of bone-targeted agents to modify the process of metastasis has been studied extensively. Many adjuvant trials with bisphosphonates in early breast cancer have been performed. Variable outcomes in terms of disease recurrence have been reported, with any treatment benefits apparently influenced by the age and menopausal status of the patients. Results show that in breast cancer the use of adjuvant bisphosphonates reduce bone metastases and breast-cancer deaths in postmenopausal women. These effects are in addition to the benefits associated with the use of standard adjuvant endocrine, cytotoxic and targeted treatments with prevention of one in six breast-cancer deaths at 10years. Biomarkers that can predict patient benefit from the use of bone-targeted treatments in the adjuvant setting are being evaluated. Currently, tumour expression of the transcription factor, MAF, seems to be the most promising biomarker; benefits from adjuvant bisphosphonates are seen in the 80% of patients with normal levels of expression irrespective of menopausal status and age, while over expression is associated with a poor prognosis and a higher rate of visceral metastases. Adjuvant bisphosphonates are now part of standard clinical guidelines for postmenopausalwomen with early breast cancer at intermediate to high risk of recurrence. MAF testing of primary tumours may improve patient selection for treatment.

Bisphosphonate and its impact on orthodontic tooth movement

In orthodontic treatment, mechanotherapy is needed to move the teeth. It is a challenge for the dentist to maximize the desired tooth movement without losing anchorage. Some experts have proposed a mechanical device to prevent the loss of anchorage, but it is still common to lose anchorage and cause side effects such as root resorption, white spots, caries, gingivitis and others. The use of bisphosphonates is recommended for the control of relapse and even for establishing pharmacological anchors. Bisphosphonates are pharmacological agents used to treat osteoporosis patients. This pharmacological agent is a potential bone resorption inhibitor. So, the use of bisphosphonates can be useful for orthodontist to control anchorage movement. Many literatures have begun to discuss the use of BP in orthodontic treatment patients. This review article aims to analyze the literature that discusses the influence of BP on orthodontic tooth movement.

Time-varying exposure to anti-osteoporosis drugs and risk of first-time hip fracture: a population wide study within the Norwegian Epidemiologic Osteoporosis Studies (NOREPOS)

SummaryWe investigated the association between bisphosphonate and denosumab use and risk of hip fracture in Norway. These drugs protect against fractures in clinical trials, but their population-level effect is unknown. Our results showed lowered risk of hip fracture for treated women. Treatment of high-risk individuals could prevent future hip fractures.PurposeTo investigate whether bisphosphonates and denosumab reduced the risk of first-time hip fracture in Norwegian women when adjusting for a medication-based comorbidity index.MethodsNorwegian women aged 50–89 in 2005–2016 were included. The Norwegian prescription database (NorPD) supplied data on exposures to bisphosphonates, denosumab, and other drugs for the calculation of the Rx-Risk Comorbidity Index. Information on all hip fractures treated in hospitals in Norway was available. Flexible parametric survival analysis was used with age as time scale and with time-varying exposure to bisphosphonates and denosumab. Individuals were followed until hip fracture or censoring (death, emigration, age 90 years), or 31 December 2016, whichever occurred first. Rx-Risk score was included as a time-varying covariate. Other covariates were marital status, education, and time-varying use of bisphosphonates or denosumab with other indications than osteoporosis.ResultsOf 1,044,661 women 77,755 (7.2%) were ever-exposed to bisphosphonate and 4483 (0.4%) to denosumab. The fully adjusted hazard ratios (HR) were 0.95 (95% confidence interval (CI): 0.91–0.99) for bisphosphonate use and 0.60 (95% CI: 0.47–0.76) for denosumab use. Bisphosphonate treatment gave a significantly reduced risk of hip fracture compared with the population after 3 years and denosumab after 6 months. Fracture risk was lowest in denosumab users who had previously used bisphosphonate: HR 0.42 (95% CI: 0.29–0.61) compared with the unexposed population.ConclusionsIn population-wide real-world data, women exposed to bisphosphonates and denosumab had a lower hip fracture risk than the unexposed population after adjusting for comorbidity. Treatment duration and treatment history impacted fracture risk.

Does Perioperative Use of Bisphosphonate Affect the Implant Revision Rate of Total Ankle Arthroplasty?

It is unknown whether perioperative bisphosphonate (BP) use reduces revision rates in total ankle replacement arthroplasty (TAR) although its effect has been demonstrated to be effective in reducing revision rates in total knee or hip replacement arthroplasty. We reviewed National Health Insurance Service data based on national health insurance service claims data and health care utilization, health screening, sociodemographic variables, medication history, operation codes, and mortality data for 50 million Koreans. From 2002 to 2014, 6391 of 7300 patients who underwent TAR were BP nonusers, whereas 909 patients were BP users. The revision rate according to BP medication and comorbidities was investigated. The Kaplan-Meier estimate and extended Cox proportional hazard model were also used. The revision rate of TAR was 7.9% for BP users and 9.5% for BP nonusers, which showed no significant difference (P = .251). Implant survival over time decreased constantly. Adjusted hazard ratio for hypertension was 1.242 (P = .017), whereas other comorbidities such as diabetes had no effect on the revision rate of TAR. We found that the perioperative BP use did not reduce the revision rate of TAR. Comorbidities (except hypertension) did not affect the revision rate of TAR. More research regarding various factors affecting the revision of TAR could be warranted. Level III, retrospective cohort study.

P082 Research priorities regarding the use of bisphosphonates for osteoporosis: a UK priority setting exercise

Abstract Background/Aims Worldwide, many people who would benefit from osteoporosis treatment are not offered or receiving them, resulting in an osteoporosis care gap. Adherence with bisphosphonates is particularly low. This study aimed to identify stakeholder research priorities relating to bisphosphonate regimens for the treatment of osteoporosis. Methods A three-step approach based on the James Lind Alliance methodology for identification and prioritisation of research questions was used. Research uncertainties were gathered (Step 1) from recent published international clinical guidelines and a large programme of related research studies about bisphosphonate regimens: the ‘Bisphosphonate aLternAtive regimenS for the prevenTion of Osteoporotic Fragility Fractures’ (Blast Off) study, which consisted of six discrete individual research studies conducted between May 2019 and February 2022, relating to the experience, effectiveness and cost-effectiveness of different bisphosphonate regimens. Clinical and public stakeholders refined the list of uncertainties into research questions (step 2) and then prioritised the questions using a modified nominal group technique (step 3) in two, day-long online workshops. Results In total, 34 draft uncertainties were finalised into 33 research questions by stakeholders. Twenty nine stakeholders were involved in refining uncertainties and prioritisation, including 16 public contributors, 2 Allied Health Professionals, 3 GPs and 8 Consultants. The top 10 questions are shown in Table 1. Conclusion This study reports, for the first time, topics of importance to stakeholders in the research of bisphosphonate osteoporosis treatment regimens. The priorities address how to better implement guidelines to address the care gap, understanding patient factors influencing treatment selection and effectiveness, and how to optimise long-term care. These findings have implications for research into implementation to address the care gap and education of healthcare professionals in the treatment of osteoporosis. Disclosure Z. Paskins: None. A. Moult: None. N. Corp: None. A. Bastounis: None. S. Davis: Grants/research support; Grant from Roche Diagnostics to her employing insitution to fund research into the cost-effectiveness of using a biomarker to monitor response to treatment with antifracture medication. M. Narayanasamy: None. J. Griffin: None. N. Gittoes: None. J. Leonardi-Bee: None. T. Langley: None. S. Bishop: None. O. Sahota: None.

Examination of Risk Factors and Expression Patterns of Atypical Femoral Fractures Using the Japanese Adverse Drug Event Report Database: A Retrospective Pharmacovigilance Study.

Atypical femoral fracture (AFF) is a rare complication related to the use of bisphosphonates (BPs). Herein, we analyzed the risk factors and onset patterns of AFF using the Japanese Adverse Drug Event Report database and reported the findings. First, the independent risk factors for AFF were gender (female), high body mass index, and medical history of osteoporosis, arthritis, and systemic lupus erythematosus (SLE). Drug-related risk factors for AFF included BPs (i.e., alendronic acid, ibandronic acid, etidronic acid, zoledronic acid, minodronic acid, risedronic acid), denosumab, prednisolone, lansoprazole, rabeprazole, exemestane, letrozole, eldecalcitol, and menatetrenone. Therefore, it appears that AFF is influenced by a combination of patient backgrounds and drugs, and that the risk of developing AFF is particularly high in patients with fragile bones (e.g., osteoporosis, arthritis, and SLE). Second, in the analysis of AFF onset patterns, the onset of AFF from BPs and denosumab took a long time (>1 year) to develop. Analysis using a Weibull distribution showed wear-out failure-type AFF onset for BPs and denosumab, and both osteoporosis and cancer patients with long-term administration of these drugs showed a tendency to have an increased risk of onset. AFF developed earlier in osteoporosis patients with long-term administration of BPs and denosumab than in cancer patients.

Denosumab and incidence of type 2 diabetes among adults with osteoporosis: population based cohort study

ObjectiveTo estimate the effect of denosumab compared with oral bisphosphonates on reducing the risk of type 2 diabetes in adults with osteoporosis.DesignPopulation based study involving emulation of a randomized target...

Osteonecrosis of the jaw with the use of bisphosphonates and treatment with laser therapy and magnetotherapy: a concise systematic review

Introduction: Bisphosphonate-related osteonecrosis of the jaw (BRONJ) has been increasing, mainly as a consequence of the treatment of osteoporosis in elderly women. During bone resorption, bisphosphonates (BP) are taken into osteoclasts and exhibit cytotoxicity, producing a long-lasting anti-bone resorptive effect. several energy-based devices have been used with substantial clinical improvement in the treatment. Devices are widely used in various types of treatment, such as LASER, LED, TEMs, infrared devices, Ultrasound, and radiofrequency, among others. Objective: It was to analyze the main findings and weave approaches of scientific evidence of the occurrence of osteonecrosis by the use of bisphosphonates, as well as the possible treatments, highlighting laser therapy and magnetotherapy. Methods: The present study was followed by a systematic review model (PRISMA). The search strategy was performed in the PubMed, Cochrane Library, Web of Science and Scopus, and Google Scholar databases. The Cochrane Instrument was used to assess the risk of bias from the included studies. The present study was carried out from December 2022 to March 2023. Results and Conclusion: A total of 138 articles were found. Initially, duplicate articles were excluded. After this process, the abstracts were evaluated and a new exclusion was performed based on the GRADE Instrument and Risk of Bias. A total of 58 articles were fully evaluated and 26 were included and discussed in this study. It was concluded that photobiomodulation therapy and magnetotherapy showed safety and efficacy in the treatment of BRONJ, through the reduction of phlogistic signs, faster healing, and reduction of postoperative morbidity. Only four applications of low-intensity laser and magnetotherapy were enough to reduce the inflammatory process in the surgical wound, stimulate the tissue repair process and provide postoperative analgesia.

Therapeutic strategy for atypical ulnar fracture in long use of bisphosphonate: A systematic review

BackgroundAtypical fractures are caused by the combined effects of severe suppression of bone metabolism (SSBT) due to long-term bisphosphonate therapy and chronic repetitive bone microdamage. Atypical ulnar fractures (AUFs) due to SSBT are rare, and there is no standard treatment strategy for such fractures. The relevant literature was reviewed, and the treatment strategy for AUF is discussed. MethodsA systematic review was conducted. All studies on ulnar fractures in individuals with a history of bisphosphonate use were included, and the data were extracted and analyzed from the perspective of the therapeutic strategy. ResultsForty limbs of 35 patients were included. As for the treatment of AUF, 31 limbs were treated surgically, and conservative treatment with casting was performed for 9 limbs. The bone fusion rate was 22/40 (55.0%), and non-union was seen in all patients treated conservatively. There was a significant difference in the bone fusion rate between patients with surgical treatment and those with conservative treatment. The bone fusion rate of patients with parathyroid hormone (PTH) and surgery was 82.3% (14/17 limbs); the bone fusion rate with PTH and bone graft was 69.2% (9/13 limbs). However, there were no significant differences in the fusion rate in the groups with or without PTH, with or without bone grafting, or the combination of the two treatments. There was also no significant difference in the bone fusion rate in the groups with or without low-intensity pulsed ultrasound (LIPUS) treatment. ConclusionsBased on the literature review, surgery is necessary to achieve bone union, but surgery alone is not adequate to achieve bony union. Bone grafting and the administration of PTH and LIPUS may promote early bone fusion, but the present study did not show significant advantages of these additional treatments for bone union.

Relationship of the occurrence and main approaches to osteonecrosis of the jaw with the use of bisphosphonates: a concise systematic review

Introduction: In the setting of bucomaxillo facial surgery, bone tissue is a specialized connective tissue made up of cells and a mineralized extracellular matrix. To reduce the excessive resorption observed in these pathologies, it has been studied more rigorously in pre-clinical and clinical studies to improve anti-resorptive drugs that allow for treating or preventing pathologies of bone metabolism, such as bisphosphonates (BP) and denosumab (DN) as well as some angiogenesis inhibitors, can induce osteonecrosis of the mandible (ONJ). Objective:Foi realizar uma revisão sistemática concisa a respeito da relação da ocorrência e principais abordagens da osteonecrose da mandíbula e/ou maxilar com o uso dos bifosfonatos. Methods: The present study was followed by a systematic review model (PRISMA). The search strategy was performed in the PubMed, Cochrane Library, Web of Science and Scopus, and Google Scholar databases. The Cochrane Instrument was used to assess the risk of bias from the included studies. The present study was carried out from December 2022 to January of 2023. Results and Conclusion: A total of 108 articles were found. Initially, duplicate articles were excluded. After this process, the abstracts were evaluated and a new exclusion was performed based on the GRADE Instrument and Risk of Bias. A total of 55 articles were fully evaluated and 22 were included and discussed in this study. The American Association of Oral and Maxillofacial Surgeons proposed for the first time its nomenclature "Bisphosphonates Related Osteonecrosis of the Jaws". ONJ is the term used to describe bone cell death when the osteocyte becomes necrotic. Osteonecrosis of the jaws can be considered a severe adverse effect of BP therapy. Osteonecrosis of the jaws induced by the use of antiresorptive drugs commonly occurs in the oral cavity, mainly because the bone tissue is covered and protected only by a thin layer of periosteum and epithelium. Bisphosphonates inhibit RANKL expression, as well as stimulate OPG production by bone marrow cells and osteoblasts, inhibiting the RANK-RANKL interaction. These synergistic actions lead to a decrease in the recruitment of osteoclasts and, consequently, to a reduction in bone resorption.

Use of bisphosphonates in bone pathology – benefits and risks

This article aims to establish, on the basis of medical literature and of the authors’ experience, whether bisphosphonates still have a role in treating skeletal diseases, with increased bone resorption. The effects of bisphosphonates on the bone tissue, as well as the diseases in which they are recommended and the benefits obtained are reviewed. Possible side effects are emphasized, both the immediate ones, which are better known and the late ones, occurring after a long-term administration. It is shown that the benefit/risk ratio remains favorable. The conclusions highlight the fact that nowadays bisphosphonates still have an important place in the treatment of skeletal diseases.

A retrospective analysis of nonresponse to denosumab after hip fractures

Denosumab is an effective antiresorptive drug commonly prescribed for the treatment of osteoporosis. However, some patients do not respond well to denosumab treatment. The aim of this study was to evaluate the factors underlying treatment nonresponses to denosumab in elderly patients following hip fracture. This retrospective study included 130 patients treated with denosumab after osteoporotic hip fracture between March 2017 and March 2020. The patients were categorized as denosumab nonresponders if they had a T-score &lt;−3 that persisted between dual-energy X-ray absorptiometry scans, a &gt;3% decrease in bone mineral density (BMD), or an incident fracture on denosumab therapy. We examined the baseline characteristics associated with blunted BMD responses and compared the groups following denosumab treatment for 12 months. Of 130 patients with baseline data, 105 patients (80.8%) were considered responders. No difference in baseline vitamin D, calcium, BMI, age, gender, prior fracture history, or bisphosphonate use was observed between responders and nonresponders. A longer interval between denosumab injections was associated with suboptimal BMD response at both spine and total hip (p&lt;0.001 and p=0.04, respectively). The overall L-BMD and H-BMD were significantly increased compared with pretreatment levels after denosumab treatment (5.7% and 2.5%, respectively). This study revealed that nonresponse was not strongly associated with certain baseline variables and it appears that the reponders and nonresponders were reasonably comparable in this study population. The results of our study highlight the importance of timely denosumab administration when using this drug for osteoporosis management. Physicians should keep these results in mind in clinical practice so that they can improve utilization of 6-month denosumab.

Glucocorticoid-induced osteoporosis in premenopausal women: management for the rheumatologist.

This review seeks to summarize the literature relevant to the treatment of glucocorticoid-induced osteoporosis in premenopausal women; an issue commonly encountered by rheumatologists and yet lacking good clinical practice guidelines. Although most of the relevant literature on osteoporosis includes postmenopausal women only, data from both randomized controlled trials and case reports suggest bisphosphonates can be an effective and well tolerated treatment for premenopausal patients. Data for other medications to treat premenopausal osteoporosis is less robust. The use of bisphosphonates in young women may be safer than initially thought and should likely be used for the treatment of glucocorticoid-induced osteoporosis in rheumatology clinics. Further research is needed to continue to understand long-term risk.