Patients Receiving Bisphosphonate Therapy Research Articles

Imaging aspects of maxillomandibular bone alterations in patients with multiple myeloma treated with bisphosphonates: A systematic review.

Multiple myeloma (MM) is a rare cancer that is typically managed with bisphosphonates to slow bone resorption and prevent skeletal complications. This study aimed to identify imaging patterns in MM patients receiving bisphosphonate therapy. This systematic review included studies investigating maxillomandibular bone alterations based on imaging examinations in MM patients treated with bisphosphonates. The selected studies were qualitatively assessed using the Critical Appraisal Tools from SUMARI. Six studies, involving 669 MM patients, were included, with 447 receiving bisphosphonate treatment. The majority were treated with pamidronate, zoledronate, or a combination of both. Seventy patients developed medication-related osteonecrosis of the jaw (MRONJ), predominantly in the mandible, characterized by the presence of bony sequestrum, bone sclerosis, increased periodontal ligament space, osteolytic lesions, and osteomyelitis as observed in imaging analyses. For non-MRONJ lesions, the mandible also exhibited the highest frequency of asymptomatic bone alterations. These ranged from "punched-out" osteolytic lesions or "soap bubble" lesions to solitary bone lesions, areas of bone sclerosis, abnormalities of the hard palate, osteoporosis, non-healed alveoli, and cortical bone rupture. MM patients treated with bisphosphonates display radiographic patterns of maxillomandibular bone lesions. These patterns aid in diagnosis and facilitate early and targeted treatment, thereby contributing to improved morbidity outcomes for these patients.

Dental implants in breast cancer patients receiving bisphosphonate therapy

This review article aims to assess the success of dental implants in breast cancer patients receiving bisphosphonate therapy, and to evaluate the risk of developing bisphosphonate related osteonecrosis of the jaw following dental implant surgery.Breast cancer patients undergoing bisphosphonate therapy may receive dental implants. However, the risk of developing BRONJ and implant failure is quite high. Risk factors such as the type of BP received, the route of administration, and the length of treatment prior to surgery should be considered.

Hyperbaric oxygen therapy as a conservative approach for osteoradionecrosis of the jaw in an osteoporotic patient receiving oral bisphosphonate therapy: a case report

BackgroundOsteoradionecrosis of the jaw (ORNJ) is a well-known chronic side effect of radiotherapy (RT) for head and neck malignancies. Osteonecrosis of the jaw (ONJ), similar pathology to ORNJ, may be induced by bisphosphonate (BP) therapy and is known as BP-related ONJ (BRONJ). Although differences exist between ORNJ and BRONJ in terms of clinical features and management methods, ONJ in a patient with history of both RT and BP therapy is categorized as ORNJ in the diagnostic criteria, despite the possibility that the ONJ may be affected by BP considering the pharmacology and mechanism of action. To date, management of ORNJ with a history of BP therapy has been scarcely discussed.Case presentationWe report here our experience of serious ORNJ in an 82-year-old osteoporotic woman receiving oral BP therapy. She had undergone partial maxillectomy to treat left maxillary gingival cancer and had received RT of 60 Gy as postoperative treatment. She had a history of osteoporosis, for which she had been administered BP for 8 years and 5 months. A bony sequestrum 45 × 25 mm in size was found at the site of the mandibular ramus, and the clinical diagnosis was ORNJ. We administered hyperbaric oxygen therapy (HBOT), scheduled for 3–5 days per week in 2 courses, 35 times. After HBOT, we performed sequestrectomy avoiding invasive surgery such as mandibulectomy. After the surgical procedure the wound healed completely. Bone regeneration was confirmed by computed tomography postoperatively. There have been no signs of recurrence as of 4 years after the operation.ConclusionsWe undertook a multimodality approach with HBOT and conservative surgery and achieved a satisfactory outcome. HBOT may be worthy of consideration as a conservative approach for ORNJ in patients receiving BP therapy, leading to the possibility of avoiding invasive surgery such as mandibulectomy.

Magnetic Resonance Imaging Signal Changes Mimicking Bone Metastasis in Patients Receiving Bisphosphonate Therapy

Bisphosphonates are inorganic pyrophosphate agents that reduce bone turnover. These agents reduce bone pain and delay skeletal complications, such as fractures in patients with metastatic lytic lesions, malignant-related hypercalcemia, multiple myeloma, Paget’s disease of bone, and osteoporosis. Osteonecrosis, developing in the jaw bones specifically, has been described as a complication associated with the use of bisphosphonates. In this report, we presented osteonecrosis-like magnetic resonance imaging findings that can be confused with bone metastasis in two patients who underwent long-term bisphosphonate treatment and the value of bone scan and 18flor-fluorodeoxyglucose positron emission tomography/computerized tomography in the differential diagnosis.

Dental extractions in patients on oral or intravenous bisphosphonate therapy: A clinical dilemma

Dental extraction has been touted to be a potential trigger for the onset of bisphosphonate-related osteonecrosis of the jaw (BRONJ). In this article, we carry out a comprehensive discussion on the pharmacology of bisphosphonates. This article also aims to assess and outline the pathogenesis of BRONJ, the outcome of dental extractions on patients receiving bisphosphonate therapy and to draw a protocol for its prevention and management.

ПРИМЕНЕНИЕ АУТОЛОГИЧНОЙ ПЛАЗМЫ ПРИ ЛЕЧЕНИИ МЕДИКАМЕНТОЗНО АССОЦИИРОВАННОГО ОСТЕОНЕКРОЗА ЧЕЛЮСТЕЙ

Subject. Drug-associated jaw osteonecrosis is a serious complication that can occur in patients receiving bisphosphonate therapy for bone metastases in malignant neoplasms. The studies are due to the widespread use of bisphosphonates in patients with proven bone metastases, with myeloma, and malignant neoplasms of various locations. Due to the toxic effects of bisphosphonates on soft tissues, the healing process is sluggish, often with a relapse. The task of finding optimal methods of stimulating local regenerative processes is urgent, since the use of general-action drugs can provoke continued growth of the primary tumor. The aim of the study was to develop a method for treating patients with a diagnosis of “drug-associated jaw osteonecrosis” using autologous plasma, which will further reduce the number of relapses and increase the effectiveness of treatment. Methodology. Patients with a diagnosis of “medically associated jaw osteonecrosis” underwent sequestrectomy with boundaries determined by perfusion by laser Doppler flowmetry, an APRF clot was placed on the bottom of the bone wound, and autologous plasma was injected into the wound edges in the postoperative period. Results. The result of applying this technique in the early postoperative period was a partial discrepancy of the edges of the wound, but the absence of sections of the exposed bone in the wound. After 6–8 weeks, we observed complete healing of the postoperative wound. The number of relapses was reduced from 16 to 3 (by 57.56 %). Conclusions. The use of autologous plasma in the treatment of drug-associated osteonecrosis is the most optimal way to stimulate local regenerative processes in the absence of the possibility of using general-action drugs.

Лазерная доплеровская флоуметрия - метод определения границ секвестрэктомии при бисфосфонатном остеонекрозе челюсти

osteonecrosis of the is a severe complication that can occur in patients receiving bisphosphonate therapy due to bone metastases. The relevance of research is conditioned by spread use of bisphosphonates in patients with proved bone metastases in myeloma. Despite the active study of the problem, a high percentage of relapses of the disease remains, the direct criteria of sequestrectomy determination lines during surgical treatment. The study was conducted on the basis of the Department of maxillofacial surgery MAI CCCH №23”, where patients with the diagnosis of Bisphosphonate osteonecrosis of the jaw in the period from December 2017 to December 2018 were treated.

Atypical femur fractures in patients receiving bisphosphonate therapy: etiology and management.

Osteoporosis is a growing problem that is projected to affect more than 50% of American adults by 2020. Bisphosphonate therapy is currently the primary mode of treating osteoporosis in this population. While bisphosphonate therapy has been successful in increasing bone mineral density, data has shown an increased risk of atypical femur fractures with prolonged therapy. Atypical femur fractures are characterized by low-energy or atraumatic injuries that occur in the subtrochanteric region. They originate on the medial cortex, travel transversely, and typically have little or no comminution. Conservative therapy is indicated for patients with incomplete fractures without prodromal symptoms. Patients with incomplete fractures and significant prodromal symptoms or visible fracture line on radiographs, those who have failed conservative management, and those with complete fractures should be treated with intramedullary nail fixation. Evaluation should involve imaging of the contralateral femur. Teriparatide therapy may be considered for patients without contraindications. While the incidence of these fractures is low, it is likely that these rates will increase with the aging population and increased prevalence of patients being treated with bisphosphonate therapy.

Atypical periprosthetic acetabular fracture in long-term alendronate therapy.

Bisphosphonates have been commonly used in the treatment of osteoporosis, demonstrating its efficacy in fracture risk reduction. However, even if are generally safe and well tolerated, concerns have emerged about atypical fractures related to its prolonged use. Although atypical femoral fracture are more common, case reports demonstrated that even other skeletal areas can be involved by unusual pattern of fracture. We report a atypical acetabular periprosthetic fracture in a 83-year-old female patient after prolonged alendronate treatment for osteoporosis and isolated acetabular revision surgery. The patient underwent to clinical, bioumoral and radiological evaluation and all the history cases were fully reported. We believe this periprosthetic fracture, according to the available data, may have similar underlying pathology to atypical femoral fractures. Awareness of symptoms, in addition to a regular radiographic survey may facilitate early diagnosis and possible prevention of spontaneous periprosthetic fractures, in patients receiving bisphosphonate therapy beyond 5 years. The treatment of this atypical periprosthetic fracture should include both surgical than pharmacological therapy to obtained bone healing.

“Bisphosphonates: Possible Modes of Action and Implications for Dental Implant Treatment. A Review of the Literature”

Bisphosphonates (BP) have been commonly used over the past 40 years to treat osteoporosis, Pagets’ disease, hypercalcemia of malignancy, osteolytic lesions of multiple myeloma and bone metastases associated with breast, prostate, lung and other soft tissue tumours. The main aims of this review are to: 1. Highlight the fundamental pharmacophysiological modes of action of both nitrogen and non-nitrogen bisphosphonates on bone 2. Explore their potential effects on oral hard and soft tissues 3. Discuss the implications of bisphosphonate therapy on dental implants, in particular their contribution to implant failure 4. Discuss the current recommendations and guidelines for dental implant therapy in patients receiving bisphosphonate therapy based on the available evidence. Two distinct types of bisphosphonates have been classified and differentiated according to their mode of action, chemical structure, potency, delivery, bioavailability, dosage and half-life. Bisphosphonates are classified as: 1) Nonnitrogen containing bisphosphonates (BP) and 2) Nitrogen containing bisphosphonates (N-BP). 27 studies met the study inclusion and exclusion criteria, with 8 retrospective studies and 2 case series studies evaluating the success rate of dental implants in patients with a history of bisphosphonate use, while the remaining 17 articles consisted of case series and case reports. While there are shortcomings associated with many of the reported studies, there does appear to be a certain risk associated with the both implant placement and the maintanence of osseointegrated implants in patients receiving oral bisphosphonates. A Southern Austrailian study estimated the risk of implant failure in patients receiving oral bisphosphonates to be 0.88%. Late implant failures appear to occur in patients treated with oral bisphosphonate exposure for a period >3 years especially in patients who have existing integrated implants,while early failures appear to occur in patients treated with bisphosphonates before or at the time of implant placement. Although the results from these retrospective studies and case series are conflicting to some extent, they have heightened awareness of the possible complication of BRONJ and bisphosphonate related implant failure from long term bisphosphonate use, be it oral or iv-bisphosphonates.

Cytoprotective effects of melatonin on zoledronic acid-treated human mesenchymal stem cells in vitro

ObjectiveBisphosphonate-related osteonecrosis of the jaw (BRONJ) is a common clinical complication in patients receiving bisphosphonate therapy. Furthermore, melatonin has been proposed as a therapeutic drug for the oral cavity due to its antioxidant properties. This study aimed to evaluate the cytoprotective effects of melatonin on zoledronic acid (ZA)-treated human mesenchymal stem cells from periodontal ligament (PDLSCs) and bone marrow (BMMSCs). MethodsPDLSCs and BMMSCs were exposed to ZA, melatonin or ZA + melatonin for 72 h. Cell proliferation was measured by a colorimetric assay, whereas their mesenchymal phenotype was analyzed by flow cytometry. ResultsProliferation assays showed that BMMSCs presented higher ZA resistance than PDLSCs, as well as a difference in response to the simultaneous treatment of ZA + melatonin. Using PDLSCs, high doses of melatonin significantly increased their proliferation, whereas lower concentrations were enough to enhance ZA-treated BMMSC proliferation. Moreover, PDLSCs displayed a CD90/CD105 downregulation and CD73 upregulation in response to ZA, which was more pronounced in response to melatonin. Furthermore, ZA or ZA + low doses of melatonin induced a decrease of expression of CD90/CD105/CD73 on BMMSCs, while a higher concentration recovered CD73 levels. ConclusionThese results suggest that melatonin has a cytoprotective effect on ZA-treated PDLSCs and BMMSCs. Thus, it could be used for BRONJ prevention.

Tooth extraction in patients receiving oral or intravenous bisphosphonate administration: A trigger for BRONJ development?

IntroductionScientific debate outlines tooth extraction as a potential trigger for the onset of bisphosphonate-related osteonecrosis of the jaw (BRONJ). Therefore, the aim of this study was to investigate the outcome of tooth extractions in patients receiving bisphosphonate therapy. Patients and methodsA retrospective cohort study was performed on patients with a history of oral or intravenous bisphosphonate administration and tooth extraction between 2007 and 2013 in a single university hospital oral and maxillofacial surgical unit. In all patients, extractions were performed according to the guidelines of the German Society of Oral and Maxillofacial Surgery. The outcome variable was the onset of typical BRONJ signs during postoperative follow-up. ResultsIn 72 subjects (53 female, 19 male; mean age 67.5 years) receiving oral (n = 27) and/or intravenous (n = 45) bisphosphonates due to malignant tumor (n = 43) or osteoporosis (n = 29), 216 tooth extractions were performed. The mean duration of intake was 36.2 months. In 67 out of 72 patients (93.1%) and 209 out of the 216 extraction sites the postoperative course was uneventful and the wounds healed without complications. Three of the 72 patients (4.2%) developed osteonecrosis of the jaw in four of the 216 extraction sites (1.9%). Duration and route of administration, oral hygiene and steroid intake were identified as potential risk factors for the development of BRONJ. ConclusionTooth extraction in patients receiving bisphosphonates can be performed in a safe and predictable way, even in high-risk patients, when performed according to established guidelines. It is not tooth extractions themselves, but rather prevailing infectious conditions that may be a key risk factor for the development of BRONJ.

Bone Hyperplasia at the Alveolar Bone Crest around Implants in Three Patients Receiving Bisphosphonate Therapy

Bone Hyperplasia at the Alveolar Bone Crest around Implants in Three Patients Receiving Bisphosphonate Therapy

Effect of intravenous hydration in patients receiving bisphosphonate therapy.

Patients with advanced cancers are at high risk for bone metastases, which accelerate bone resorption and skeletal complications. Therefore, bisphosphonates, which are strong inhibitors of bone resorption, are widely used to prevent pathological fractures, pain and tumour-induced hypercalcaemia. Intravenous infusion of bisphosphonate is associated with dose- and infusion rate-dependent adverse renal effects. The present study investigated the effect of hydration on bisphosphonate efficacy and safety. The 600-bed CHOV Hospital (Neufchâteau, France) and the Université de Lorraine (Nancy, France). Patients who received pamidronate or zoledronic acid treatments were identified: 50 patients [16 of whom were hydrated and 34 of whom were non-hydrated]. Data on serum calcium levels, creatinine clearance and clinical tolerance were collected. Main outcome measure The impact of hydration on these parameters was analysed between day 1 and day 7. Bisphosphonate normalized calcaemia and hydration did not induce further reduction of calcium levels. Patient kidneys were significantly preserved by hydration in both groups (median clearance: +6.2%), whereas dehydrated patients had lower creatinine clearance (median clearance: -1.1%). Hydration did not influence other clinical or biological parameters tested. Hydration plays an important role in the treatment of hypercalcaemia by pamidronate and zoledronic acid: it enhances kidney protection (i.e., creatinine clearance).

Current controversies in classification, management, and prevention of bisphosphonate-related osteonecrosis of the jaw.

Current controversies in classification, management, and prevention of bisphosphonate-related osteonecrosis of the jaw.

Femoral insufficiency fractures with bisphosphonate therapy – cases studies

The aim of this paper is to analyze on clinical cases specific features of femoral insufficiency fractures during bisphosphonates therapy. We are presenting two insufficiency femoral fractures (2 patients) in patients receiving bisphosphonate therapy. These two cases represent new type of femoral fractures. These are low energy or spontaneous fractures of diaphysis and subtrochanteric region. Prodromal pain is often observed. On x-rays thick lateral cortex, its ellipsoid thickening and transverse or oblique fracture line is observed. Many authors link such fractures to long-term bisphosphonate therapy. Patients on long term bisphosphonate therapy present with new and specific fracture pattern of femoral bone. Fractures of this pattern are extremely rare. The risk benefit ratio of bisphosphonates therapy is not changed.

Prevalence of jaw osteonecrosis among patients receiving bisphosphonates in Riyadh

The objective of this study is to obtain data on the prevalence of bisphosphonate-associated osteonecrosis of the jaws (ONJ) among patients who received dental treatment in Riyadh.The study was conducted in five hospitals in the Riyadh area. All subjects were interviewed to collect data regarding their medical history, bisphosphonates usage, dental history, and possible complications after dental treatment. A total of 88 subjects under bisphosphonates therapy were interviewed, 25% were males and 75% were females. Bisphosphonates were taken orally by 89.7% of the subjects while 10.2% received bisphosphonate intravenously. All the subjects have had dental treatments after the beginning of bisphosphonate therapy. 79.5% of those patients had dental extraction, 13.6% root canal treatment, 4.5% oral surgery, and 4.5% received dental implants. No complications were reported after the dental treatment.In the present study, patients with bisphosphonates therapy did not develop complication after the dental treatment. However, it is recommended that patients receiving bisphosphonate therapy should be treated with precaution. Dental awareness programs should be provided to the physicians prescribing bisphosphonates to their patients.

Diagnosis of Proximal Femoral Insufficiency Fractures in Patients Receiving Bisphosphonate Therapy

The purpose of this article is to describe the imaging features of proximal femoral insufficiency fractures in patients on long-term bisphosphonate therapy. The imaging findings of bisphosphonate-related femoral insufficiency fractures, which include a typical proximal diaphyseal location and transverse liner radiolucency through localized thickening of the lateral cortex, allow a specific diagnosis.

An Observational Study of Musculoskeletal Pain Among Patients Receiving Bisphosphonate Therapy

To seek evidence for the association of bisphosphonate use with diffuse musculoskeletal pain (MSKP) in a large national cohort, controlling for conditions associated with MSKP. This retrospective cohort study enrolled all US veterans aged 65 years or older with a vertebral or hip fracture who were treated for at least 1 year between October 1, 1998, and September 30, 2006 (N=26,545). All International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) diagnostic codes, demographics, and pharmaceutical data were obtained from national databases. A composite end point, based on ICD-9-CM codes compatible with diffuse MSKP, was constructed. The primary outcome was time until MSKP. We performed regression analysis using the Cox proportional hazards model, controlling for age, sex, race, alcoholism, depression, anxiety, smoking, recent 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor (statin) use, rheumatic disease, and comorbidity score. The univariate regression identified an association of bisphosphonate exposure and MSKP (hazard ratio, 1.22; 95% confidence interval, 1.04-1.44). In the multivariate regression, however, patients prescribed a bisphosphonate were not more likely to be assigned an ICD-9-CM code compatible with diffuse MSKP (hazard ratio, 1.10; 95% confidence interval, 0.93-1.30). Consistent with prior studies, we found that female sex, depression, anxiety, comorbidity score, and the presence of a rheumatic disease were all associated with a greater risk of a diagnosis of diffuse MSKP. There was no demonstrable association with statin exposure. Bisphosphonate use was not associated with a statistically higher rate of MSKP in this cohort. Individual patients may rarely report MSKP while taking bisphosphonates; however, for our studied cohort, incident MSKP does not appear to explain bisphosphonate discontinuation rates.

Unusual mid‐shaft fractures during long‐term bisphosphonate therapy

Bisphosphonates are the most commonly prescribed medications for the treatment of osteoporosis. Although existing evidence supports a good safety profile, there is concern that chronic administration of these agents could result in severe suppression of bone turnover with increased risk of nonvertebral fractures. The objective of this study was to report the clinical presentation, selected bone histomorphometry and X-ray images of patients who developed mid-shaft long bone fractures during bisphosphonate therapy, six of whom had bone biopsy for histomorphometery. Of the 13 patients who sustained atraumatic mid-shaft fractures, 10 were on alendronate and three were on risedronate therapy before the fractures. In addition to bisphosphonates, three patients were on oestrogen and two on tamoxifen concomitantly. Four patients with glucocorticoid-induced osteoporosis were on alendronate for 3-11 years along with glucocorticoid therapy. Bone histomorphometry showed severe suppression of bone turnover in five patients and low bone turnover in one patient. Long-term bisphosphonate therapy may increase the risk of unusual long bone mid-shaft fractures. This is probably due to prolonged suppression of bone turnover, which could lead to accumulation of microdamage and development of hypermineralized bone. At present, the scope of this complication in the larger context of patients receiving bisphosphonate therapy remains unknown, but appears to be small.