Oral Bisphosphonates For Osteoporosis Research Articles

THU446 A Case Of Isolated Osteonecrosis Of Torus Palatinus In A Patient On Alendronate

Abstract Disclosure: A.A. Noor: None. A. Zia: None. B. Hoard: None. K. Romo: None. S. Bhamre: None. M. Gabriel: None. S. Shu: None. R. Ozolins: None. T. Pulisetty: None. G.I. Uwaifo: None. Introduction: Osteonecrosis of the jaw (OJN) is a rare complication of bisphosphonate and RANKL inhibitor use. Most cases have been described in cancer or immunocompromised patients using high dose parenteral therapy, but have even more rarely been described with oral bisphosphonate (OBP) use. The estimated risk is 1 in 10,000 to 1 in 100,000 patient-years in patients taking OBP for osteoporosis. We describe a case isolated osteonecrosis of torus palatinus (OTP) in a patient with long-term use of OBP (alendronate) for postmenopausal osteoporosis. Case Report: 75-year-old female with a history of torus palatinus (TP), osteoporosis, fibromyalgia, echondromas of humerus, degenerative disc disease, and spinal stenosis initially presented at a primary care clinic with three weeks of inflamed, painful, red, and swollen oral ulcer; associated with exudative tonsillitis. She finished an antimicrobial course which improved tonsillitis, but the oral ulcer persisted. She was on alendronate 70 mg weekly for ∼ three years prior to symptom onset. Examination showed a nearly 1 cm shallow ulcer on the left aspect of her large TP with associated erythema and tenderness to palpation. The rest of the oral cavity was normal. She was given triamcinolone paste for two weeks. Follow-up 1 month later showed progression of ulcer down to bone underlying the TP. The mucosa of the TP was erythematous, thickened, and tender. Given the lack of resolution after antimicrobials and topical steroids, a biopsy was done which showed squamous mucosa with reactive changes, hyperkeratosis, and chronic inflammation, but negative for dysplasia or malignancy. Maxillofacial CT showed, “a lobulated bony mass in the roof of the mouth consistent with TP with left-central heterogeneous density and cortical bone thinning without soft tissue mass or extension. Due to suspicion for osteomyelitis and possible underlying malignancy, lesion excision, and debridement was done. Alendronate was stopped at this point. Excisional biopsy showed necrotic bone consistent with OTP with associated acute and chronic osteomyelitis. She was treated with four weeks of metronidazole and two weeks of fluconazole. The postoperative course was uneventful, with appropriate healing. Conclusion: While OJN is uncommon in setting of OBP use, among patients with TP and other bone overgrowth states high index of suspicion is needed for bony lesions developing in such patients. The possibility of OTP development should be considered with appropriate oral complaints among OBP users with TP. Further retrospective analyses to ascertain how prevalent this uncommon condition is would provide much needed clinical information. Presentation: Thursday, June 15, 2023

P02 When should we stop the antiresorptive medications in patients with osteoporosis?

Abstract Introduction Bisphosphonates are first line and denosumab is the latest antiresorptive agent approved for osteoporosis treatment. Those drugs showed a reduction in vertebral fracture risk and other non-vertebral by 35-70%. One of the rare adverse events with antiresorptive treatment is medicine-related osteonecrosis of jaw (MONJ) which mainly occur in individuals receiving high doses for the treatment of cancer. Recent research found true incidence of MONJ is very low despite public perception. Studies indicate that 50% of women and 20% of men aged over 50 years will experience an osteoporosis-related fracture which have significant associated morbidity and mortality. Case description We report a case of an osteoporosis patient who was treated with alendronate followed by denosumab and presented with suspicion of MONJ. In 2014, a 77-year-old female was referred following right neck of fragility femur fracture. DXA showed osteoporosis (T- score of the spine −3.2, T- score total hip −2.4 and T- score of left neck of femur −2.1). She was initially treated with four years of alendronate (70 mg once weekly) but sustained a pubic rami fracture. Hence, she was then treated with six monthly injections of denosumab (60 mg subcutaneously). After three injections, she developed jaw pain. She was reviewed by her dentist who advised her to stop the denosumab for suspected MONJ. She was then seen by the oral surgeon who confirmed that there was a piece of bone in UR6 socket but with no bone sequestrum and this piece of bone was removed under local anaesthesia with good healing. She was advised to restart denosumab. The patient was extremely worried and anxious about denosumab recommencement and teriparatide was considered. After completion of teriparatide treatment her DXA still showed osteoporosis (T- score of the spine −2.1, T- score of total hip −2.2 and T- score of left neck of femur −2.6) with stable changes in the hip and improvement in the spine. On review, she continued to have concerns about antiresorptive treatment. Further oral surgeon review stated low grade infection around UL7 with poor gum condition around UR6 and LR6 with some bleeding points but no definite diagnosis of MRONJ. It was advised that any further manoeuvre involving tooth extraction will be conducted by the oral surgeon. Following this, the patient was happy to consider zoledronic acid infusions. She is due for her 3rd zoledronate infusion and is undergoing regular dental checks. Discussion The incidence of MONJ in patients taking oral bisphosphonates for osteoporosis is relatively low, estimated to be less than 1% (0.001% to 0.01%). However, the risk is higher for individuals receiving higher doses of intravenous bisphosphonates for the treatment of cancer or bone-related complications of cancer. The incidence of MONJ in cancer patients receiving intravenous bisphosphonates ranges from 1% to 15%. More clinical studies have been published that describe the relation between MONJ and denosumab in cancer patients with the risk of MONJ varying between 0.7 to 1.9% (70 to 90 cases per 10,000 patients). However, in patients with osteoporosis treated with denosumab, the incidence of MONJ is lower, resulting in an even lower frequency of 0.04% (4 cases per 10,000 patients). It is understandable that there is a significant concern amongst dentists about MONJ risk with antiresorptive treatment, but it is paramount that the patients are made aware of the fracture risk and its significant effect on quality of life. Many patients are not aware that more than 20% of patients die in the first year after a hip fracture from complications surrounding the fracture and a significant number of patients lose their long-term ability to live independently. Vertebral fractures have significant morbidity and the mortality rate of 72% at 5 years and 90% at 7 years. Key learning points Most dentists are often reluctant to treat patients on anti-resorptive medications due to the risk of MONJ which results in patient’s concerns about treatment and subsequent stoppage of osteoporosis treatment leading to fracture risks. Thus, it is imperative to assure the patients of benefits of the anti-resorptive medications versus the MONJ risks. This calls for increased awareness and national guidelines for the prevention and management of ONJ in osteoporosis patients treated with antiresorptive.

Anti-osteoporotic medication and scleroderma

Scleroderma (systemic sclerosis) represents a challenging condition, usually requiring a multi-disciplinary team due to multi-organ involvement; it is mostly considered an autoimmune disease; the signature of the malady is the extensive fibrosis at the level of skin and multiple organs, associating endothelial/vessel damage and anomalies of immune response. We point out a few aspects concerning scleroderma-related osteoporosis. This is a literature review. Patients might associate low bone mineral density (the underling mechanisms are not entirely understood), thus an increased risk of fractures; so early recognition and treatment is mandatory for a better outcome. Some data showed that particularly vertebral fractures are prone to the condition. Almost half of individuals with the malady have osteoporosis (female prevalence, especially post-menopausal) and one third of them have an osteoporotic fracture. Older age and associated vitamin D deficiency increases the risk of fracture. Vitamin D has pleomorphic distribution, also targeting the immune modulation, cytokines puzzle, and the muscle-bone crosstalk in scleroderma. Hypovitaminosis D might be expected in these patients, while general D-supplementation has controversial benefits effects. Chronic inflammatory rheumatic conditions might benefit from the TBS use as fracture risk indicator through micro-architecture evaluation. It seems that patients with systemic sclerosis and malnutrition have lower TBS; high Dkk-1 serum levels (Dickkopf-1) is correlated with reduced TBS and advanced disease; TBS is correlated to the extent of microvascular complications; exposure to glucocorticoids (certain high-dose regimes) supplementary lowers TBS. Gastrointestinal complications are presented in 90% of patients with systemic sclerosis, involving fibrosis at any level which is a poor prognostic factor; malabsorption of nutrients and weight loss correlates with reduced bone formation while esophageal and gastric anomalies contraindicate the use of oral bisphosphonates for osteoporosis. Other abnormal elements of skeleton frame include: premature ovarian failure, serotonin system anomalies, chronic inflammation, potential side effects of immunosuppressant drugs. In patients with systemic sclerosis, the choices of medication targeting osteoporosis are limited; the use of intravenous bisphosphonates remains first line option (if renal function is adequate); the consideration of skin and esophageal anomalies is mandatory in the management of osteoporosis. Overall, the landscape of bone domain in systemic sclerosis is multi-leveled and some areas are still waiting for clear answers.

Oral bisphosphonates for osteoporosis in adult males with intellectual disabilities.

Oral bisphosphonates are first-line agents for treating osteoporosis in men, but there are no studies regarding efficacy of oral bisphosphonates for treatment of osteoporosis in ambulatory male adults with intellectual disability. Nine adult males with intellectual disability and increased fracture risk had been treated with weekly or monthly oral bisphosphonates, vitamin D and calcium for 1-3years. Post-treatment bone mineral density (BMD), serum 25(OH)D, parathyroid hormone and C-telopeptide of type I collagen were then determined for the first time. Weekly or monthly oral bisphosphonates were well tolerated and led to significant increases in BMD in all 9 individuals. Serum 25(OH)D level enhanced the "pecent increase of BMD" that occurred in response to bisphosphonate treatment (p<.05). Weekly or monthly oral bisphosphonates are well tolerated by ambulatory adult males with ID and are effective in increasing BMD. Higher serum levels of vitamin D appear to improve the efficacy of bisphosphonates and therefore reduce fracture risk in adult males with intellectual disability.

Real-world persistence and adherence with oral bisphosphonates for osteoporosis: a systematic review

ObjectivesThis study examined patient adherence and persistence to oral bisphosphonates for the treatment of osteoporosis in real-world settings.MethodsA systematic review was completed according to the Preferred Reporting Items for Systematic...

The incidence of Bisphosphonate related Osteonecrosis of the Jaw (BONJ) in patients treated with oral bisphosphonates for osteoporosis

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Bisphosphonate-related osteonecrosis of the jaw: awareness and level of knowledge of Lebanese physicians.

Bisphosphonate-induced osteonecrosis of the jaw (ONJ) is a potentially destructive complication, particularly encountered in oncology. It is supposed that awareness and good knowledge of this disease by physicians are important factors of its early detection and management. This study aims to evaluate the level of knowledge among a sample of Lebanese physicians with regard to this complication. An observational cross-sectional study was conducted at Hôtel-Dieu de France hospital between March and June 2013. Data were collected through a self-administered questionnaire distributed to 190 eligible physicians in the departments involved in prescribing bisphosphonates and managing the ONJ. A total of 136 valid responses were obtained (response rate 71.6 %). Eighty-six (63.2 %) physicians were treating patients with bisphosphonates: the most prescribed form being the weekly oral bisphosphonates for osteoporosis followed by zoledronate several times yearly for bone malignancies. Fifty-one (37.5 %) participants were unaware of bisphosphonate-related ONJ. Furthermore, the level of knowledge was relatively poor: the mean score of all participants was 12.42 ± 10.08, while 77 (56.6 %) had a global score more than 16 over 30. There were statistically significant associations between the level of knowledge and physicians' specialty (p value <0.0001), whether or not they prescribe bisphosphonates (p value = 0.039), the most frequently form prescribed (p value = 0.048), whether or not they attend patients already on bisphosphonate (p value = 0.047), whether or not they have observed (p value = 0.004) and treated (p value = 0.002) exposed necrotic bone of the jaw. Our study revealed a deficient knowledge regarding bisphosphonate-related ONJ among Lebanese physicians. Appropriate training strategies to increase their awareness are required.

The frequency of bisphosphonate related osteonecrosis of the jaws (BRONJ): a single centre prospective

The frequency of BRONJ following dental extraction in osteoporotic patients on oral bisphosphonates is of key interest to Oral and Maxillofacial Surgeons. The estimated frequency of the pathology ranges from 1 in 251, to 1 in 296 to 11302, and 1 in 952 to 15373. There is also estimated figure of 1:10000 to 100,000 suggested by the American Bone and Mineral Research Group. 4900 consecutive patients on oral bisphosphonate for osteoporosis were included in the study over a 6 years period. Detailed demographic information was recorded.

Osteonecrosis of the maxilla in a patient on ibandronate: A case report

Bisphosphonate-related osteonecrosis of the jaw (BRONJ) was initially described in 2003 [1,2]. It is a potentially serious condition characterized by exposure of bone in the mandible or maxilla, persisting for more than 8 weeks in a patient, who has taken or is currently taking a therapeutic bisphosphonate and has no history of therapeutic radiation of the jaw [3]. The incidence of BRONJ seems to be relatively low in patients receiving oral bisphosphonates for osteoporosis or Paget’s disease (1:10,000– 1:100,000) and considerably higher in patients with malignancy receiving high doses of intravenous bisphosphonates (1:10–1:100) [4]. We report an interesting case of BRONJ in osteoporotic woman, receiving ibandronate, a nitrogen-containing bisphosphonate.

Osteonecrosis associated with dental implants in patients undergoing bisphosphonate treatment

Bisphosphonate-related jaw necrosis (BRONJ) associated with dental implants is a rare but continuously reported complication. To verify clinical and pathological characteristics of BRONJ around dental implants, the present study analyzed clinical, radiographic and histopathological findings of these lesions. Nineteen patients were diagnosed with osteonecrosis of the jaw associated with dental implants and treated at our institute from 2008 to 2011. The patients' medical history, demographic features, radiographic, and histopathological findings along with information on bisphosphonates (BP) administration were analyzed. The majority of BRONJ patients associated with dental implants used oral BP for osteoporosis. The patients were divided into two groups: BP initiation before (n = 16) and after (n = 3) implant surgery. Only three patients (15.8%) could be regarded as "implant surgery-triggered" BRONJ. Many patients (n = 9) showed successful osteointegration after fixture installation to an average of 35 months (11-82 months) until the development of osteonecrosis. The histological features of the lesion showed that the necrotic bone with empty lacunae was infiltrated by inflammatory cells and bacterial colonies. Viable osteocytes were also observed in some areas of the bony specimens. Three types of bone destruction pattern were observed: (i) complete necrosis of the bone around the implant (frozen type), (ii) extensive osteolysis around the implant with or without sequestra (osteolytic type), and (iii) sequestration of bone with an implant maintaining direct implant-bone contact (en block sequestration type). These findings could be existed at the same lesions depending on the degree of local bone destruction and the severity of the infection. These results and those of others suggested that already osseointegrated dental implants can also cause the osteonecrosis around the implant after BP administration. En block sequestration of bone with implant might be one of the characteristics of implant-related BRONJ, which is different from peri-implantitis-induced bone destruction. The possible role of microcracks in this type of bone destruction needs to be examined further.

Bisphosphonates: An update

Bisphosphonates are used widely for variety of bone condition, most notably IV bisphosphonates in the treatment of metastic bone lesion and oral bisphosphonates for osteoporosis. They constitute a group of drugs capable of modulating bone turnover and reducing its remodeling when an excessive resorption occurs. In the last few years, due to their extensive use, many cases of complications associated with their use have been published. This paper provides recent knowledge on general characteristics of these drugs and their mechanism of action, pathogenesis, as well as their relevance to dentist.

Bisphosphonate-associated osteonecrosis of the jaw in rheumatology: a sistematic review

Osteonecrosis of the jaw (ONJ) is a well-known devastating side effect of parenteral bisphosphonate therapy for cancer. Several ONJ cases have been reported in patients taking oral bisphosphonates for osteoporosis or Paget's disease. Even if the number of cases of ONJ in patients taking oral bisphosphonates are still rare compared to the total exposure, rheumatologists treating bone diseases with bisphosphonates must be aware of this new complication, allowing for prevention and early diagnosis. The patients must be informed on the benefit/risk of bisphosphonate therapy and, when necessary and possible, alternative therapy for postmenopausal osteoporosis should be considered. The need for the patient to be dentally fit and to maintain this state forever should be part of the informed consent for bisphosphonate treatment. It is uncommon for rheumatologists to ask about dental problems but this new bisphosphonate- associated complication highlights the need for this to change. In this paper we review the literature available on this newly described bisphosphonate-induced complication with particular emphasis on ONJ cases related to the use of oral bisphosphonates.

Use of oral bisphosphonates and risk of venous thromboembolism: a population-based case-control study

Oral bisphosphonates are widely used for fracture prevention, but there is a concern regarding potential adverse cardiovascular effects of bisphosphonates. In this large, population-based case-control study, we found no evidence of an association between bisphosphonate use and risk of venous thromboembolism (VTE). We examined the relation between the use of oral bisphosphonates for osteoporosis and the risk of VTE. We conducted a population-based case-control study in Northern Denmark (population, 1.7 million). Using the Danish National Registry of Patients, we identified all women with a first-time hospital diagnosis of VTE between 1999 and 2006. For each case, we selected up to ten female population controls, matched on date of the index VTE event and age. Data on use of oral bisphosphonates, other medications, and comorbidity were obtained from medical databases. We used logistic regression to estimate odds ratios (OR) for VTE associated with bisphosphonate users while adjusting for potential confounding factors. Four thousand one hundred ninety-three cases and 41,197 controls were included in the study. One hundred forty-nine cases (3.6%) and 1,078 controls (2.6%) were current bisphosphonate users. The adjusted OR for VTE among the current bisphosphonate users compared with nonusers was 1.03 (95% confidence interval (CI): 0.84-1.26), and when restricted to cases of unprovoked thromboembolism, the adjusted OR was 1.08 (95% CI: 0.82-1.42). There was no association either for pulmonary embolism or for deep venous thrombosis. We found no evidence of an association of oral bisphosphonate use with the risk of VTE.

Oral bisphosphonate-related osteonecrosis of the jaw: the first report in Asia

Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a serious side effect of bisphosphonate therapy. The incidence of BRONJ is known to be low among patients treated with oral bisphosphonates. We investigated the prevalence, demographics, clinical manifestations, and treatment outcome of 24 patients with oral BRONJ in Asian populations. The long-term safety of oral bisphosphonates is clinically important considering the rare but potentially serious complications such as bisphosphonate-related osteonecrosis of the jaw (BRONJ) versus the effect of reducing and preventing osteoporotic fracture. The incidence of BRONJ is known to be low among patients treated with oral bisphosphonates around the world. However, the prevalence in those taking oral bisphosphonates for osteoporosis in Asian populations is unknown. Moreover, a recent article, showing that the majority of reported patients who received alendronate were Asian American, raised concern about the prevalence of oral BRONJ in Asian populations. The objective of this study was to investigate the estimated prevalence, clinical characteristics, and treatment outcome of oral BRONJ in Asian populations. From October 2005 to December 2008, a retrospective review of medical charts identified 24 patients receiving oral bisphosphonates diagnosed as BRONJ at the Department of Oral and Maxillofacial Surgery, Yonsei University Dental Hospital, Seoul, South Korea. The estimated prevalence of oral BRONJ was 0.05-0.07%. The average oral bisphosphonate treatment duration was 43.1 months (range, 5-120 months). Treatment with oral antibiotics and/or surgery including sequestrectomy or alveolectomy showed relatively favorable results. The prevalence of oral BRONJ in Korea is similar to that reported previously in Western populations. We suggest that recognition of BRONJ and appropriate management pre- and post-dental surgery might reduce the frequency of BRONJ among patients receiving oral bisphosphonates.

The oral health status of patients on oral bisphosphonates for osteoporosis

The oral health status of patients on bisphosphonates is the key to the patient's ongoing health and well-being. If they are orally healthy, invasive bone procedures, particularly extractions can be avoided, then the risk of osteonecrosis of the jaws (ONJ) is low. The records of 49 consecutive patients on oral bisphosphonates, referred to the Oral and Maxillofacial Surgery Unit (OMSU) for an oral health check and probable extractions, were retrospectively reviewed. The DMFT, periodontal and pathologic state were calculated from the OPG radiographs. An age and gender matched control group, from patients referred to the OMSU but who were not on oral bisphosphonates, were similarly assessed. Community data were also obtained. The DMFT score for the oral bisphosphonate group was 29: Decayed 3, Missing 10, Filled 16. The control group DMFT score was 24: Decayed 5, Missing 11, Filled 8. Both groups had advanced periodontal disease (over 95 per cent) and were medically compromised (over 90 per cent). The DMFT for general community data for age matched government pensioners was 19.1: Decayed 0.8, Missing 10.4, Filled 7.9. With severe periodontal disease 23 per cent. Thus, the oral health of the oral bisphosphonate group was similar to the control group and both had more decayed teeth and periodontal disease than community values. This study confirms that one cannot assume that a patient on an oral bisphosphonate for osteoporosis has a healthy mouth. It supports the view that all patients on bisphosphonates need to be seen by a dentist either before or soon after commencement of bisphosphonate therapy.

Continuing professional development self‐assessment quiz: The oral health status of patients on oral bisphosphonates for osteoporosis

Continuing professional development self‐assessment quiz: The oral health status of patients on oral bisphosphonates for osteoporosis

Bisphosphonate related osteonecrosis of the palate: report of a case managed with free tissue transfer

The management of patients with established bisphosphonate-related osteonecrosis of the jaws (BRONJ) remains unclear. The patient discussed here presented with spontaneous BRONJ of the palate after taking an oral bisphosphonate for osteoporosis. Conservative management resulted in progression of the osteonecrosis. Surgical debridement and immediate reconstruction with free tissue transfer was undertaken and resulted in complete resolution of her condition. The case is presented here.

Oral bisphosphonates and osteonecrosis of the jaw: are the MHRA recommendations appropriate?

The association between bisphosphonate therapy and osteonecrosis of the jaw was first reported in 2003, in patients with malignant disease who were being treated with large doses of intravenous bisphosphonates. Subsequently, possible cases of osteonecrosis of the jaw have been reported in a very small number of people taking oral bisphosphonates for osteoporosis; at the time of publication of its ‘expert panel recommendations’, the American Dental Association estimated that there were approximately 183 such cases worldwide. The word ‘possible’ is particularly apposite in the context of diagnosis of osteonecrosis of the jaw, since the disease is poorly characterized in terms of its clinical

Evaluation of Real-World Persistency With Weekly Oral Bisphosphonates for Osteoporosis

Evaluation of Real-World Persistency With Weekly Oral Bisphosphonates for Osteoporosis