Bisphosphonate Medication Research Articles

Comparison of bone turnover suppression in atypical femoral fractures and osteoporotic hip fractures

We aimed to compare the extent of bone turnover suppression between patients with atypical femoral fractures (AFFs) and osteoporotic hip fractures (typical femur fractures, TFFs) using a one-to-one matching strategy. A single-center retrospective comparison of females aged ≥ 60 years who underwent operative treatment for AFFs and TFFs between January 2010 and March 2021 was conducted. Demographic characteristics and clinical data including fracture site, past medical history, bone mineral density (BMD), bisphosphonate (BP) medication history, and serum bone turnover marker (BTM) levels were examined. Moreover, we performed a logistic regression analysis to determine the risk factors for AFFs and a one-to-one matched-pair analysis to compare various BTMs. Overall, 336 consecutive females were included: 113 with AFFs and 213 with TFFs. The mean age, BMI, and lowest BMD T-score were 78.6 years, 22.8 kg/m2, and −3.3, respectively. Patients with AFF were younger, had lower BMD, higher BMI, higher prevalence of rheumatoid arthritis, a greater proportion with previous steroid or BP use, and a longer history of BP use than patients with TFF. The 48:48 matched-pair analysis revealed higher serum 25(OH) vitamin-D (30.5 vs 18.2 ng/mL, P < 0.001) and calcium levels (8.8 vs 8.3 ng/dL, P = 0.009) and lower serum CTX levels (0.33 vs 0.54 ng/mL, P = 0.010) in the AFF group than in the TFF group, suggesting a more suppressed bone remodeling. No differences in the other BTM levels were found. Despite identical histories and durations of BP use, the AFF group exhibited lower CTX levels, suggesting more suppressed bone remodeling. This observation leads us to infer that more suppressed bone remodeling, indicated by lower CTX levels, could be linked to the occurrence of AFFs.

Farnesyl pyrophosphate synthase inhibitors with antiosteoporosis efficacy in ovariectomized rats: A mixed binding approach beyond bisphosphonates

The primary focus of bisphosphonate medications is on targeting human farnesyl pyrophosphate synthase (hFPPS), an essential regulator of mammalian isoprenoids. Yet, these drugs encounter limitations due to their restricted "druglike" properties and their effectiveness primarily in treating skeletal disorders. In this study, we synthesized novel non-bisphosphonate compounds, using 4,4'-(ethane-1,2-diylbis(oxy))bis(3-methoxybenzaldehyde) (1) as a starting compound, with the aim of targeting hFPPS through a mixed binding approach. Among the various compounds tested, compounds 4a and 4b exhibited significant inhibition of hFPPS activity, with IC50 values of 1.108 and 1.24 μM, respectively. Docking studies further revealed that both compounds bound within the allylic binding site and near the isopentenyl diphosphate (IPP) site within the hFPPS pocket. Molecular dynamic simulations were performed on the best docking pose of the most potent compound 4a to confirm the formation of a stable complex with hFPPS. In an in vivo study conducted on ovariectomized rats, various biochemical markers including osteocalcin, estradiol, osteoprotegerin, bone mineral content, and density were negatively impacted, while levels of bone specific alkaline phosphatase, receptor activator of nuclear factor kappa-Β ligand, serum/urinary calcium, and phosphate increased. Notably, compound 4a exhibited antiresorptive properties similar to zoledronate, effectively restoring most of the perturbed biochemical estimations. These findings suggest the potential of compound 4a, a non-bisphosphonate compound, as alternative therapeutic agents for combating osteoporosis.

Ozone infiltration as an adjunctive treatment to piezoelectric surgery in the management of medication-related osteonecrosis of the jaws: case series of 29 patients.

Medication-related osteonecrosis of the jaws has been reported to be associated with bisphosphonate and RANKL inhibitor medications. This prospective clinical study aimed to assess the outcomes of pre-operative ozone infiltration therapy in patients with established MRONJ. The treatment protocol for ozone applications were designed as 20 applications ozone infiltration therapy followed by surgical interventions of necrotic tissue debridement using piezoelectric surgery instruments. The evaluation of the results based on the clinical and radiologic specifications considering the necrotic lesion reduction and healing. The study included 31 lesions in 29 patients. The mean follow-up was 23.6 months. 25 lesions out of 31 healed totally without any remissions. The outcomes were not affected by any variables such as gender, age, type of pharmacological treatment, lesion location, and MRONJ staging. The statistically significant results were found among the clinical condition of the patients (p = 0.01) and administration route of medications (p = 0.004). Healing was significantly less in patients that received intra-vascular administrations. Clinical conditions of the patients were divided as osteoporosis, oncologic, and arthritis. Significantly better results were obtained in osteoporosis patients. 38% of the population experienced spontaneous sequestration with signs of improvements and the surgical interventions were canceled. According to the results, total healing of MRONJ lesions was seen in 79% patients (81% lesions). Ozone therapy and debridement with Piezoelectric surgery can be considered as a safe and beneficial adjunctive treatment alternative for osteonecrosis lesions in cases of established MRONJ.

Expert opinions on the prevalence, diagnosis and treatment choice for osteoarthritis management in Indian settings

Studies have reported the capability of bisphosphonates to delay the progression of structural deterioration associated with osteoarthritis (OA). Limited studies exist regarding OA management in India and the determinants influencing patients' decisions regarding surgical interventions. So, this study aimed to assess the prevalence, diagnostic practices, and treatment options available for OA management in Indian clinical practice with a special focus on alendronate, a bisphosphonate medication for OA pain management. The cross-sectional, multiple-response questionnaire-based study collected a survey response using a 25-item questionnaire from 276 clinicians across India. Additionally, the survey focused on determining the diagnostic practices helpful in determining osteoporosis and the preference of treatment options for OA management. Based on the responses of 276 participants, 43% indicated that the diagnosis of OA was predominant in both genders. Moreover, about 51% of the respondents suggested that mass screening for osteoporosis in Indian patients should be conducted using the one-minute risk test developed by the International Osteoporosis Foundation. Additionally, 47% of the respondents highlighted hip fractures as the most common type of bone fracture observed in these patients. Furthermore, around 51% of the study participants emphasized that adequate calcium consumption during childhood can potentially reduce the incidence of osteoporosis. For the effective management of OA, alendronate was preferred by 49% of respondents over the other bisphosphonates.As per the expert consensus,patients who have osteoporosis risk factors and osteopenia without fragility fractures were recommended to adhere to dietary and lifestyle modifications, coupled with calcium and vitamin D supplementation, and bisphosphonate therapy. Alendronate was preferred over other bisphosphonates for the effective management of OA.

Assessment of Role of Bisphosphonates on Dental Implant Treatment in Post-menopausal Ladies.

To examine the impact of bisphosphonates (BPs) on dental implant treatment and alveolar bone in post-menopausal ladies. Twenty post-menopausal ladies who had at least one dental implant within the previous 5 years participated in the current study. Ten subjects were categorized into two groups: Group A had BP medication for 1.5 years, and group B received parathyroid hormone (PTH). Both groups' bone thickness and bone mineral density (BMD) were measured. Group A had 5%, and group B had 5% of dental implants failures. BMD of cortical bone was 1468 ± 136 mg/mL and 1008 ± 84 mg/mL in groups A and B, correspondingly. The cortical and cancellous bone densities in both the groups were statically significant. Cortical bone thickness was insignificant in comparison. Both cortical and cancellous bones' bone mineral density decreased in both groups. With continued usage of BPs, the cortical bone thickness increased.

A retrospective case series on bisphosphonate related osteonecrosis of the jaw in 20 cats.

This retrospective study highlights the salient aspects of a series of feline patients affected with bisphosphonate related osteonecrosis of the jaw. Though more commonly published in human literature, this presentation is rare in cats. The authors hope that this study will assist in making this a more globally known entity with subsequent improved prognosis. Data was retrospectively obtained from the medical records between 2015 and 2021 of 20 cats with Medication Related Osteonecrosis of the Jaw. Data included patient information, clinical history, presenting complaint, systemic diseases, details referable to hypercalcemia and treatment thereof, bisphosphonate specifics (dose and duration), clinical presentation of the lesion, diagnostic testing including radiographic and histopathologic descriptions, treatment, and outcome. Pertinent results include that all 20 cats who developed Medication Related Osteonecrosis of the Jaw had been treated for idiopathic hypercalcemia with the bisphosphonate medication alendronate. Eighty-five percent of the cases had prior dental extractions at the site of MRONJ lesion. Ninety-five percent of the affected cats required a surgical procedure to control the disease. Thirty-five percent of cases required at least one revision surgery after the initial procedure was performed. Diagnosis of MRONJ was made by a correlation of diagnostic findings and patient history. No single diagnostic, or combination was pathognomonic for lesion diagnosis. As well, there were no statistically significant associations between patient variables assessed and the overall patient outcome. The case series reveals that cats with feline idiopathic hypercalcemia treated with alendronate may be at a risk for development of MRONJ, a serious oral condition with significant morbidity. Prior dental extraction sites in patients concurrently treated with bisphosphonate medications were often associated with MRONJ lesions. Therefore, any needed dental surgery should be performed prior to the use of bisphosphonates where possible. The authors have also included a relevant comparative literature review.

THU449 An Unexpected Case Of Cutaneous Leukocytoclastic Vasculitis Following Zoledronic Acid Infusion

Abstract Disclosure: B. Zahedi: None. Z.S. Wallace: None. M.M. Cote: None. E.W. Yu: Grant Recipient; Self; Amgen Inc. Background: Zoledronic acid is a potent amino-bisphosphonate frequently used in the treatment of osteoporosis. We report a case of small-vessel vasculitis with cutaneous manifestations occurring after zoledronic acid infusion, previously not reported in the literature. Clinical case: A 58-year old woman with a history of sleeve gastrectomy 1.5 years prior was treated for bone protection with an intravenous infusion of zoledronic acid (Zol) 5mg. This was the patient’s first exposure to a bisphosphonate medication. Within minutes of the infusion, she developed a single episode of diffuse watery diarrhea. Although GI symptoms resolved quickly, within a few hours she experienced generalized myalgias and skin tenderness in her abdomen and extremities, for which she took NSAIDs. These symptoms progressed in severity over the next 3-5 days, manifesting as bilateral hand and lower extremity edema and erythema; no fever/chills/sweats, mucocutaneous ulcers, or urinary symptoms were present. By Day 5, she developed palpable purpura without blanching above the ankles and extending to the knees. By Day 7, prednisone 60mg was started. Prior to Zol, labs showed sufficient 25-hydroxyvitamin D, normal calcium, renal and liver function. On Days 10 and 14, labs revealed AST and ALT, twice and thrice the upper limit of normal respectively. Other notable labs included normal UA, Ca, WBC, eGFR, nonelevated ESR/CRP, and a negative work up for an underlying infectious, inflammatory, ANCA-associated, hypocomplementemic or autoimmune process. Cutaneous findings resolved within 3 weeks of Zol, and transaminitis and edema resolved by week 4. In the setting of a negative lab workup and typical palpable purpura, the patient was diagnosed with leukocytoclastic cutaneous vasculitis (LCV), likely induced by Zol (Naranjo score of 5 consistent with probable adverse drug reaction). Although IgA-mediated Henoch-Schonlein Purpura (HSP) cannot be definitively ruled out in absence of a skin biopsy, the patient did not exhibit other clinical features of HSP, and the timeline is highly suggestive of an idiosyncratic drug reaction whereby Zol acted as a hapton to stimulate an immunologic vasculitis response. Up to 50% of patients with LCV have systemic involvement (renal, GI, pulmonary, cardiac or CNS). Cutaneous LCV usually carries a favorable prognosis after treatment with glucocorticoids. On review of the literature, no prior cases of bisphosphonate-induced LCV have been reported, although there are few cases of giant cell arteritis, uveitis and urticarial vasculitis with bisphosphonate therapy. Conclusions: This is the first case demonstrating cutaneous manifestations consistent with leukocytoclastic vasculitis due to zoledronic acid infusion, which was successfully managed with NSAIDs and glucocorticoids. Clinicians should be aware that LCV may be a rare hypersensitivity complication of Zol. Presentation: Thursday, June 15, 2023

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

Category: Ankle Arthritis; Other Introduction/Purpose: 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. Therefore, the purpose of this study was 1) to investigate whether there is a relationship between the use of BP and the revision rate of TAR, and (2) to determine the effect of BP medication period on the revision rate of TAR. Our hypothesis was that the use of BP would lower the revision rate of TAR. Methods: We reviewed National Health Insurance Service data based on national health insurance service claim data and health care utilization, health screening, socio-demographic 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 non-users, while 909 patients were BP users. The revision rate according to BP medication and co-morbidities was investigated. The Kaplan-Meier estimate and extended Cox proportional hazard model were also used. Results: The revision rate of TAR was 7.9% for BP users and 9.5% for BP non-users, which showed no significant difference (p=0.251). Implant survival over time decreased constantly. Adjusted hazard ratio for hypertension was 1.242 (p=0.017), while other co-morbidities such as diabetes had no effect on revision rate of TAR. Conclusion: We found that the perioperative BP use do not reduce the revision rate of TAR. Co-morbidities except hypertension did not affect the revision rate of TAR. More research regarding various factor affecting revision of TAR could be warranted.

Clinicians’ views of prescribing oral and intravenous bisphosphonates for osteoporosis: a qualitative study

BackgroundBisphosphonate medications, including alendronate, ibandronate and risedronate administered orally and zoledronate, administered intravenously, are commonly prescribed for the treatment of osteoporosis based on evidence that, correctly taken, bisphosphonates can improve bone strength and lead to a reduction in the risk of fragility fractures. However, it is currently unclear how decisions to select between bisphosphonate regimens, including intravenous regimen, are made in practice and how clinicians support patients with different treatments.MethodsThis was an interpretivist qualitative study. 23 semi-structured telephone interviews were conducted with a sample of general practitioners (GPs), secondary care clinicians, specialist experts as well as those providing and leading novel treatments including participants from a community intravenous (IV) zoledronate service. Data analysis was undertaken through a process of iterative categorisation.ResultsThe results report clinicians varying experiences of making treatment choices, as well as wider aspects of osteoporosis care. Secondary care and specialist clinicians conveyed some confidence in making treatment choices including on selecting IV treatment. This was aided by access to diagnostic testing and medication expertise. In contrast GPs reported a number of challenges in prescribing bisphosphonate medications for osteoporosis and uncertainty about treatment choice. Results also highlight how administering IV zoledronate was seen as an opportunity to engage in broader care practices.ConclusionApproaches to making treatment decisions and supporting patients when prescribing bisphosphonates for osteoporosis vary in practice. This study points to the need to co-ordinate osteoporosis treatment and care across different care providers.

Women's perspectives regarding osteoporosis, fracture risk, and pharmacologic treatment: a cross-sectional study.

Bisphosphonate medications can prevent the substantial bone loss that occurs during early menopause, but little is known about whether women would accept bisphosphonate treatment at this time in their life, when imminent fracture risk is low. We assessed women's perspectives regarding bone loss, fracture risk, and preventative pharmacotherapy in early menopause. In this cross-sectional study, Canadian women aged ≥ 45years were recruited via Facebook advertisement to complete an electronic survey. Primary outcome was the proportion of early menopausal respondents (≤ 5years since final menstrual period) who were worried about bone loss and fractures. Secondary outcomes were the proportionof early menopausal women willing to accept pharmacologic intervention aimed at preventingeither bone loss or future fractures. We compared responses between early menopausal women and older women (> 5years since final menstrual period). 2033 women responded to the Facebook advertisement, 1195 eligible women (aged: 45 to 89years) started the survey, and 966 completed it. Among early menopausal respondents (N = 98), 38 (42%) were worried about future fractures and 9 of 25 (36%) who had a prior bone mineral density scan were worried about their results. A total of 42 (47%) were willing to start medication to prevent fractures, and 48 (54%) would start medication to prevent bone loss. Responses were comparable between early menopausal women and older women. Menopausal women are concerned about bone loss and fractures. Many women would consider early menopausal pharmacotherapy, with the goals of preserving bone health and lowering their risk of fractures.

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.

Risk factors and management of choroidal effusions.

Choroidal effusions are recognized as a common early postoperative complication of glaucoma surgery, and although often benign, they may cause significant ocular morbidity. This article aims to summarize current research on the risk factors and management of choroidal effusions. Glaucoma drainage device (GDD) implantation and trabeculectomy are the most commonly performed surgeries for the management of moderate to severe glaucoma. Common postoperative complications of these procedures include hypotony and the development of choroidal effusions. Choroidal effusions have recently been associated with the oral administration of certain drugs, including select monoclonal antibody, antiseizure and bisphosphonate medications. Risk factors for effusion development include specific patient characteristics such as pseudoexfoliative glaucoma, older age and hypertension. Although choroidal effusions typically resolve with medical therapy alone, surgical intervention may be required. Various methods of surgical intervention, such as surgical drainage or GDD tube ligation, can be utilized to treat choroidal effusions when conservative management with medical treatment fails, but themselves carry alternative risks that must be considered. Minimizing the incidence and duration of hypotony following ophthalmic surgery and careful monitoring of patients starting certain oral medications are important in limiting the occurrence of choroidal effusions. Risk factors for choroidal effusions have been recently identified in the literature. A better understanding of these risk factors, as well as the outcomes of choroidal effusion management, can help to reduce the occurrence of effusions overall and minimize ocular morbidity.

The importance of Cone-Beam computed tomography in diagnosis of associated mandibular osteonecrosis: case report / A importância da TCFC no diagnóstico e prognóstico da osteonecrose mandibular associada aos bisfosfonatos: relato de caso clínico

The Cone-Beam Computed Tomography (CBCT) is very useful in diagnosis and treatment planning, as well as in the prognosis of osteonecrosis of the jaws. This study reports a clinical case of Bisphosphonate-Associated Mandibular Osteonecrosis from the perspective of CBCT. The patient, female, 83 years old, presented painful symptoms in the posterior region of the right mandible and reported Bisphosphonate medication for more than five years to treat osteoporosis and osteopenia. Based on clinical and CBCT imaging characteristics, the patient was diagnosed with Bisphosphonate-Associated Mandibular Osteonecrosis. Initially, the treatment consisted of oral antibiotic therapy, pain control, hyperbaric oxygenation and oral hygiene (mouthwashes). After 11 months of clinical therapy, CBCT revealed bone reconstruction of the buccal cortex, but also a hypodense imaging in the lingual cortex compatible with bone lysis and bone sequestration. The patient was referred for bone debridement and sequestrectomy. The histopathological diagnosis consisted of osteonecrosis with secondary acute osteomyelitis. After 60 days of the surgical procedure and hyperbaric sessions/systemic antibiotic therapy, an oral healthy mucosa in the region of the right mandibular body was evidenced in the intraoral examination. Cortical bone regeneration was observed on CBCT. Concluded that the use of CBCT, in this case report, makes it possible to estimate the extent of the lesion and the post-treatment outcome, assessing bone density, the presence of bone sequestration and the involvement of the involved areas. In fact, early diagnosis is essential for the success of the therapeutic approach.

523 Reduced Incidence of Fractures After Treatment with Oxandrolone in Burn Patients

IntroductionBone density loss is a significant and well documented complication after major burns. Oxandrolone and bisphosphonates have both been used successfully to mitigate this outcome. Studies show these agents reduce both short-term and long-term bone loss, but no studies have examined the long-term clinical outcomes of these agents. This study investigates long-term outcomes of treatment with oxandrolone and bisphosphonates in burn patients.MethodsWe examined a deidentified database of electronic medical records across 55 healthcare organizations including over 75 million patients. ICD 10 codes were used to identify patients with thermal or chemical burns from January 1, 2010 to December 31, 2020. We included patients who received their first dose of oxandrolone or bisphosphonate within one month of injury. Propensity score matching was used to balance patient cohorts. ICD 10 and CPT codes were used to evaluate outcomes.ResultsWe identified 280,367 patients with burn injuries during the study time period. Of these, 903 (0.32%) received at least one dose of oxandrolone and 307 (0.11%) received at least one dose of a bisphosphonate medication within 1 month of injury. Mortality was higher among matched patients receiving oxandrolone (OR: 3.146, CI: 2.224, 4.449) or a bisphosphonate (OR 3.027, CI: 1.8, 5.092). Fracture at any site and fracture of long bones were significantly lower among matched patients who received oxandrolone (OR: 0.704 CI: 0.542, 0.914, OR: 0.689, CI: 0.51, 0.931; respectively) compared to those who did not. No reduction of fractures was seen among patients who received bisphosphonates (p >0.05). Among patients receiving oxandrolone acute kidney failure was increased (OR: 1.941, CI: 1.454, 2.592) compared to those not receiving the medication but chronic kidney failure was reduced (OR: 0.513, CI: 0.351, 0.749). There was no increase in acute or chronic kidney failure among patients receiving a bisphosphonate (p >0.05). Liver injury was not increased among patients receiving either medication (p >0.05).ConclusionsOxandrolone and bisphosphonate medications have been well studied and shown to decrease bone density loss after burn injury. Fractures of all bones and specifically long bones were reduced in patients receiving oxandrolone, suggesting that decreased bone catabolism during the acute recovery period may provide long-term injury protection. While we do see an increase in mortality with both of these medications, there is no we do not see any increase in liver failure or chronic kidney failure suggesting that factors unrelated to the administration of these medications are driving the increased mortality and may be related to selection bias. This is the first study to show that oxandrolone decreases the incidence of fractures after burn injury.

Bisphosphonate treatment is associated with decreased mortality rates in patients after osteoporotic vertebral fracture.

Osteoporotic vertebral fracture (OVF) is the most common type of fragility fracture. Bisphosphonate (BP) medication was suggested to have positive effects on both fracture prevention and recovery outcomes. The aim of this study is to investigate the effect of BP on mortality after OVF. This cohort study involved 535 patients (170 males and 365 females), aged ≥ 65years (mean age: 82.6 ± 7.0years, mean follow-up periods: 33.0 ± 25.8months) who were hospitalized after OVF from January 2011 to December 2019 at a public hospital. Patients treated with PTH (parathyroid hormone), PTH or PTHrp analogues, denosumab, and selective estrogen receptor modulators were excluded. Kaplan-Meier survival curves on mortality of patients with OVF with and without BP treatment were prepared, and log-rank tests were performed. Cox proportional hazards model was used to identify factors associated with mortality after OVF. This study included 163 (30.5%) patients treated with BP. Kaplan-Meier survival curves showed that the mortality rate after OVF was significantly lower in patients treated with BP (P < 0.001). Cox proportional hazards model showed that older age (hazard ratios [HR] = 1.066; 95%CI:1.035-1.103), male sex (HR = 2.248; 95%CI:1.427-3.542), malnutrition (geriatric nutritional risk index < 92) (HR = 1.691; 95%CI:1.005-2.846), BP medication (HR = 0.593; 95%CI: 0.361-0.976), and Japanese Orthopaedic Association score at discharge (HR = 0.941; 95%CI: 0.892-0.993) were significantly associated with all-cause mortality after OVF. BP medication is beneficial not only for fracture prevention but also for mortality after OVF.

Is the Mandibular Condyle Involved in Medication-Related Osteonecrosis of the Jaw? Audit of a Single Tertiary Referral Center and Literature Review

Background: Medication-related osteonecrosis of the jaw (MRONJ) may manifest as exposed mandible bone. Recent reviews of the incidence of MRONJ report primarily as exposed cortical bone of the mandibular body, ramus, and symphysis with no reports of condylar involvement. Objective: The aim of this study is to analyze the topographical incidence of MRONJ, comorbidities, demographics data, and clinical characteristics of patients diagnosed with MRONJ between 2014 and 2019 in the Maxillo-Facial Surgery Department University of Campania “Luigi Vanvitelli”, and compare these results with published reports. Methods: Data on 179 patients were collected for the study, including gender, age, underlying malignancy, medical history, and specific lesion location-identifying premaxilla and posterior sectors area involvement for the maxilla and symphysis, body, ramus, and condyle area for the mandible. A literature review was performed in order to compare our results with similar or higher sample sizes and find if any condylar involvement was ever reported. The research was carried out on PubMed database identifying articles from January 2003 to November 2020, where MRONJ site distribution was discussed, and data were examined to scan for condylar localization reports. Results: 30 patients had maxillary MRONJ, 136 patients had mandibular MRONJ, and 13 patients had lesions located in both maxilla and mandible. None of the patients reported condylar involvement, neither as a single site nor as an additional localization. Literature review results were coherent to our findings showing no mention of condylar MRONJ. Conclusion: Results do not show reports of condylar involvement in MRONJ. Although the pathophysiology of the disease has not been fully elucidated, two possible explanations were developed: the first one based on the condyle embryogenetic origin; the second one based on the bisphosphonate and anti-resorptive medications effects on the different vascular patterns of the mandible areas.

The incidence of medication-related osteonecrosis of the jaw following tooth extraction in patients prescribed oral bisphosphonates.

Aims To determine the incidence of medication-related osteonecrosis of the jaw in patients prescribed oral bisphosphonate medication following dental extraction in a dedicated clinic within the Department of Oral Surgery of King's College Hospital. The effect of factors such as sex, duration of therapy, medical comorbidities and site of extraction, which have previously been reported to significantly affect the risk of developing osteonecrosis of the jaw, was also examined.Materials and methods Data were gathered from the dental records of patients who had extractions over an eight-year period and were included in this retrospective study. Patients with previous or current exposure to intravenous bisphosphonates, denosumab, novel-targeted chemotherapies used in the oncology setting or radiotherapy to the head and neck were excluded from this study.Results The incidence of medication-related osteonecrosis of the jaw following tooth extraction in this group of 652 was 0.8%. A significantly increased risk of developing medication-related osteonecrosis of the jaw was evident in patients prescribed oral bisphosphonates for four years or more (p = 0.02), with an incidence in this group of 1.6%.Conclusion This study demonstrates that, following dental extraction, patients who are prescribed oral bisphosphonates are at risk of developing medication-related osteonecrosis of the jaw and that this risk increases significantly when the patient has been taking the bisphosphonate for four years or more.

Bone Mineral Density Remains Stable in Pyruvate Kinase Deficiency Patients Receiving Long-Term Treatment with Mitapivat

Bone Mineral Density Remains Stable in Pyruvate Kinase Deficiency Patients Receiving Long-Term Treatment with Mitapivat

Efficacy and safety of Duhuo Jisheng Decoction add-on bisphosphonate medications in patients with osteoporosis: A meta-analysis of randomized controlled trials

Ethnopharmacological relevanceDuhuo Jisheng Decoction (DHJSD) is the most frequently prescribed herbal formula for the treatment of osteoporosis. However, efficacy and safety of DHJSD add-on bisphosphonate medications remain unclear. Aim of the studyThe purpose of this study was to reveal efficacy and safety of DHJSD add-on bisphosphonate medications in patients with osteoporosis through a systematic review with meta-analysis of randomized controlled trials (RCTs). MethodsFive important databases were searched for RCTs on this topic, and two authors individually extracted information and data concerning study design, baseline characteristics, efficacy rate, bone mineral density (BMD), pain score, and adverse event. Meta-analysis was done mainly with risk ratio (RR) and standardized mean difference (SMD) for BMD and pain, using random-effects model; while Peto odds ratios (PORs) were used for pooling adverse event rates due to sparse data. Point estimate was reported with 95% confidence intervals (CIs). ResultsSeventeen RCTs (n = 1526) met eligibility criteria, and were included in this synthesis. Pooled estimates demonstrated that as compared with no DHJSD, DHJSD-B led to significantly higher efficacy rates (RR = 1.25, 95%CI: 1.19–1.31; I2 = 0%), more lumbar BMD (SMD = 0.61, 95%CI: 0.25–0.96; I2 = 20%), lower pain score (SMD = −1.10, 95%CI: 1.40–0.79; I2 = 33%), and lower overall adverse event rates (POR = 0.40; 95%CI: 0.20–0.97; I2 = 27%). ConclusionAdding DHJSD on bisphosphonate medications seems to be an effective and safe strategy in treating patients with osteoporosis.

Educational program for orthopedic surgeons' influences for osteoporosis.

BackgroundIn this retrospective study, we studied the impact of educational osteoporosis program on the rates of bone mineral density (BMD) assessment and bone turnover markers (BTM) and drug medications in the patients with hip fracture.MethodsThis retrospective research enrolled 651 patients aged ≥50 years who experienced hip fractures from January 2013 to December 2015. We recorded whether patients had received BMD assessment, BTM measurement, and anti-osteoporosis therapy during the period of hospitalization. Orthopedic surgeons were classified into the trained group and the untrained group. The rates of BMD assessment, BTM measurement, and anti-osteoporosis medications in the patients with hip fracture were compared between the trained group and the untrained group.ResultsBMD assessment was performed in 109/220 patients in the trained group and 142/431 patients in the untrained group. BTM measurements were performed in 130 patients in the trained group and 124 patients in the untrained group. Forty eight patients in the trained group and 63 patients in the untrained group received bisphosphonate medications.ConclusionsAlthough the rates of BMD assessment, BTM measurement, and bisphosphonate use in the patients after hip fractures are still insufficient, education programs help to improve the situation.