Long-term Use Of Oral Bisphosphonates Research Articles

Over half of seniors who start oral bisphosphonate therapy are exposed for 3 or more years: novel rolling window approach and patterns of use.

The purpose of this study was to identify and describe patterns of long-term oral bisphosphonate use among seniors using a novel methodological approach that considers extended follow-up. Among Ontarians aged 66years or older, we identified subjects with a first dispensing of alendronate or risedronate between November 2000 and December 2016. We followed them until death or December 2019 to identify patients with ≥ 3years of bisphosphonate use, defined as a proportion of days covered ≥ 80%, using 3-year rolling windows. We calculated the proportion of patients with long-term therapy (≥ 3years of use) using Kaplan-Meier estimates. We described patterns of long-term use and compared patient characteristics between patients with and without long-term therapy. We identified 260,784 eligible seniors initiating bisphosphonate therapy. Of these, 60% continued therapy ≥ 3years (77% women), and 48% continued ≥ 5years. Characteristics did not meaningfully differ between patients with or without long-term therapy. The median length of long-term therapy was 7.0 (IQR 5.1) years for women and 6.1 (IQR 4.3) years for men. Only 20% experienced a treatment gap before long-term therapy, yet 50% experienced a treatment gap of ≥ 120days after a median 5.3years of therapy. Eighty-one percent who returned to therapy following a treatment gap re-initiated an oral bisphosphonate, with 18% switching to denosumab. Among seniors initiating oral bisphosphonates, we found that 60% receive at least 3years of therapy when using an extended follow-up. Studies are needed to examine the benefits and harms of continuing bisphosphonate therapy beyond 3years.

Long-Term Use of Oral Bisphosphonates and Fracture Risk in Men with Traumatic Spinal Cord Injury

Long-Term Use of Oral Bisphosphonates and Fracture Risk in Men with Traumatic Spinal Cord Injury

Long-term oral bisphosphonate use in relation to fracture risk in postmenopausal women with breast cancer: findings from the Women's Health Initiative.

The aim of the study was to examine the association of long-term oral bisphosphonate use, compared with short-term use, with fracture risk among postmenopausal women with breast cancer. We studied 887 postmenopausal women who were enrolled to the Women's Health Initiative from 1993 to 1998, diagnosed with breast cancer after enrollment, and reported current oral bisphosphonate use of 2 years or more on a medication inventory administered in 2008 to 2009. The outcome of any clinical fracture was ascertained by self-report on an annual study form; a subset of fractures was confirmed with medical records. Women were followed from completion of the medication inventory until 2014. The association between duration of bisphosphonate use reported on the medication inventory and fracture was estimated using multivariate Cox proportional hazards survival models that compared 4 to 7 years and 8 or more years of bisphosphonate use with 2 to 3 years of use. On average, women were 76 years of age and were followed for 3.7 (SD 1.1) years. There were 142 clinical fractures. In the multivariate-adjusted analysis for fracture risk factors, 8 or more years of bisphosphonate use was associated with higher risk of fracture compared with 2 to 3 years of use (hazard ratio, 1.67 [95% CI, 1.06-2.62]). There was no significant association of 4 to 7 years of use with fracture. Bisphosphonate use of 8 or more years was associated with higher risk of any clinical fracture compared with 2 to 3 years of use. Our findings raise concern about potential harm or decreased effectiveness of long-term bisphosphonate use on fracture risk. The findings warrant confirmatory studies.

When is enough, enough?

Mrs Kim is a cheerful 63-year-old who has been agreeable to any treatment plan you have proposed. Her initial presentation was complex. Her maxillary left canine was extracted in adolescence; consequently, there was a significant maxillary-to-facial midline discrepancy of 4 mm. Bilateral fixed bridges have replaced the absent mandibular first molars. The patient had mild bimaxillary protrusion, with facial convexity that only slightly exceeds ethnic norms. Despite Mrs Kim's lip incompetence, few would have considered her unattractive. To add to the treatment complexity, there was 50% generalized crestal bone loss that preexisted her treatment course, but her periodontist considered her status to be stable. Also of note is her long-term use of oral bisphosphonates to treat osteoporosis. You elected to initiate her treatment without extractions. As treatment progressed, you gave Mrs Kim thorough autonomy by discussing the option of premolar extractions to coordinate her midlines and provide incisor retraction. Her consistent response was, “Whatever you think, doctor. I truly trust you.” But at today's debonding appointment, you feel a bit disturbed. Although she proclaimed her delight with the treatment result, her maxillary midline remains conspicuously deviated to the left and mild protrusion remains. She appreciates the excellent alignment your therapy has provided and confirms her commitment to long-term retention to maintain her result. Is there justification for your own dissatisfaction with her treatment outcome? After all, from a dental health perspective, you've successfully managed a periodontally susceptible patient who is on prolonged bisphosphonate therapy—both of which had the potential to increase the risk and complexity of treatment. And an extraction strategy would have involved replacement of both mandibular fixed bridges—a costly endeavor that she is not prepared to face. Mrs Kim is happy with the result. You had been forthright by repeatedly explaining the shortcomings of the nonextraction plan. How much information about her treatment result should you tell her without undermining her satisfaction? Are you obligated to offer any explanation of her treatment's shortcomings to fulfill your ethical responsibility? Should her less-than-perfect outcome remain as an emotional burden to you—especially since she has been such a conscientious patient? The relationship between a patient and the doctor is one of fiduciary responsibility, comprising trust that the commitment between the doctor and the patient will be upheld.1Rule J. Veatch R.M. Autonomy and informed consent.in: Bywaters L. Harmon L. Ethical principles in dentistry. 2nd ed. Quintessence, Chicago2004: 142Google Scholar By definition, this involves fidelity, but the ethical principles of veracity, beneficence, and nonmaleficence also pertain. As one component of the fiduciary relationship, the patient expects that the doctor will deliver a level of care to the best of his or her ability and be truthful regarding all aspects of treatment. Yet “truth” can often involve not only what is said, but also what is unsaid. Omission of selected details of a treatment result can be misleading or deprive patients of certain aspects of their status that may have future pertinence. For example, is explaining a posttreatment marginal ridge discrepancy between the mandibular first and second molars relevant to a patient? Is your inability to fully correct a unilateral Class II molar relationship or a 60% overbite pertinent? Such a distinction between the relevant and the irrelevant, or the trivial and the consequential, can form a fine line indeed. Mrs Kim knows nothing about the instability of proclined incisors and is unconcerned about her facial-to-maxillary midline discrepancy. She is delighted that her 2 mandibular fixed bridges do not need to be replaced. And her periodontist is pleased with her recent examination and charting results, confirming that her condition has remained stable despite her 2-year treatment course. Since you have fully disclosed her present status and its shortcomings—and she accepts both—have you fulfilled your ethical duty to maintain your fiduciary responsibility? Perhaps. But at the very least, your obligation to participate in her long-term maintenance will follow you for years to come.

Adherence to oral bisphosphonates and the risk of subtrochanteric and femoral shaft fractures among female medicare beneficiaries.

Previous studies have shown an association between duration of bisphosphonate use and atypical femur fractures. This cohort study showed an increasingly higher risk of subtrochanteric and femoral shaft fractures among those who were more adherent to oral bisphosphonates. Long-term use of oral bisphosphonates has been implicated in an increased risk of atypical femur fractures located in subtrochanteric and femoral shaft regions. Another measure of drug exposure, medication adherence, however, has not been investigated. Among all Medicare fee-for-service female beneficiaries from 2006-2010, we followed 522,287 new bisphosphonate users from their index prescription until being censored or having a primary diagnosis of closed subtrochanteric/femoral shaft or intertrochanteric/femoral neck fractures. Data about radiographs of fracture site and features were not available. Adherence was classified according to the medication possession ratio (MPR) as the following: MPR < 1/3 as less compliant, MPR ≥ 1/3- < 2/3 as compliant, and MPR ≥ 2/3 as highly compliant. Alternative cutoff points at 50 and 80% were also used. Survival analysis was used to determine the cumulative incidence and hazard of subtrochanteric/femoral shaft or intertrochanteric/femoral neck fractures. There was a graded increase in incidence of subtrochanteric/femoral shaft fractures as the level of adherence increased (Gray's test, P < 0.001). The adjusted hazard ratio (HR) for the highly compliant vs. the less compliant was 1.23 (95% Confidence Interval [CI] 1.06-1.43) overall, became significant after 2 years of follow-up (HR = 1.51, 95% CI 1.06-2.15) and reached the highest risk in the fifth year (HR = 4.06, 95% CI 1.47-11.19). However, age-adjusted incidence rates of intertrochanteric/femoral neck fractures were significantly lower among highly compliant beneficiaries, compared to less compliant users (HR = 0.69, 95% CI 0.66-0.73). Similar results were obtained when the cutoff points for being compliant and highly compliant were set at 50 and 80 %, respectively. Subtrochanteric/femoral shaft fractures, unlike intertrochanteric/femoral neck fractures, are positively associated with higher adherence to long-term (≥3 years) oral bisphosphonates in the elderly female Medicare population.

Unusual case of a conservatively treated pathological fracture after sequestrectomy in a patient with long-term oral bisphosphonate use

Bisphosphonates are used in the management of metastatic bone disease, Paget’s disease of bone and osteoporosis. A long-term complication of these drugs is bisphosphonate-related osteonecrosis of the jaws (BRONJ). Treatment of BRONJ can be quite challenging, and remains a topic of debate. We report the case of a 74-year-old woman who had used Fosamax ® (alendronate sodium) orally for four years. After 3½ years she developed pain, swelling, and a fistula in the left mandible. After exploration and sequestrectomy in combination with antibiotic treatment, osteolysis with a pathological fracture developed. Given the extent of the disorder and a decrease in complaints after the surgery, a non-surgical approach was chosen with continuation of the antibiotic treatment for 10 weeks, a soft diet and not wearing of dentures. During follow-up complaints subsided, the intra-oral fistula disappeared and the fracture healed. This is the first report of healing of a BRONJ patient stage III with pathological fracture. It illustrates the remaining healing potential of the bisphosphonate-treated bone.

Nonresolving Osteomyelitis of the Maxilla and Maxillary Sinus after Long-term Use of Oral Bisphosphonates

AbstractBisphosphonate-related osteonecrosis of the jaw (BRONJ) is a complication of Bisphosphonate (BP), medications used for treatment of osteoporosis, multiple myeloma and cancer bone metastasis. Manifestations of BRONJ include bone necrosis, exposure to the oral cavity, inflammation suppuration and pain with nonspecific radiographic changes.Case historyA 64-year-old woman had been treated with oral BP since 1991 for arthritic pain and osteoporosis. There were no other medical problems, no other medications used, she did not smoke nor drink alcohol.In 2005, the left maxillary molars had been extracted. The extraction site failed to heal, but she continued to use BP. Eighteen months later she presented with swelling and pain, suppuration and an area of 2 x 1 cm of exposed necrotic bone in the left posterior maxilla and oroantral fistula (OAF).Panoramic radiograph showed partial opacification of the maxillary sinus, unhealed extraction site, and sclerosis of adjacent maxillary alveolus. Histopathological analysis diagnosed osteomyelitis associated with actinomycosis, consistent with BRONJ.TreatmentBP was discontinued, followed by 7 months of PO antibiotics and iodoform gauze packs. The wound seemed to be completely closed but within 2 months signs and symptoms and OAF recurred. Treatment continued with antibiotics daily rinses and weekly irrigation with Chlorhexidine 2%, and several repeated sequesterctomies, however, the patient still had pain. A course of 30 hyperbaric oxygen treatment was administered. Three years from onset symptoms improved, and sequstered bone is no longer visible. However, the OAF is still present, requiring irrigations, and the radiographs still present bony abnormality.An unusually severe BRONJ of 3 years duration associated with 15 years oral BP use is presented.

Effect of Long‐Term Oral Bisphosphonates on Implant Wound Healing: Literature Review and a Case Report

Bisphosphonates suppress osteoclast activity, and their intravenous use has been reported in hundreds of cases to be associated with osteonecrosis in the jaw. Little is known of the risks associated with long-term use of oral bisphosphonates despite their use for >10 years by an oral mode of delivery for the treatment of osteopenia, osteoporosis, and Paget's disease of bone. The purpose of this report is to review the literature associated with bisphosphonate use that could impact bone healing and to report a case of bone necrosis in a patient on long-term oral bisphosphonates. A Medline search was carried out to find relevant articles from both medical and dental literature between 1960 and 2006. A patient, who had been taking an oral bisphosphonate for >10 years, developed unexplained clinical signs of bone necrosis after routine dental implant placement. This case was followed, documented, and the treatment of the osteonecrosis described. A summary of how bisphosphonates may play a role in wound healing is presented. The compromised healing noted in a patient, who was under long-term oral bisphosphonate use, was successfully treated with systemic antibiotics, local microbial mouthrinse, and aggressive defect management (detoxification and mixture of bone graft and tetracycline). This case suggests that patients under long-term oral bisphosphonate use should be treated with caution. Well-controlled, prospective clinical trials on the effect of oral bisphosphonates on bone are warranted to determine which patients may be at risk for such complications.