Incidence and Predictors of Fragility Fracture in Postmenopausal Rheumatoid Arthritis Patients Receiving Oral Bisphosphonates: A Longitudinal Observational Study

Background: Although many studies have reported the predictors of fractures in patients with rheumatoid arthritis (RA) who are not receiving anti-osteoporotic treatments or who are receiving unspecified treatments, studies focusing on the predictors of fracture in patients with RA who are currently being treated with oral bisphosphonates (BP) are quite scarce. This study aims to investigate the incidence and predictors of fragility fracture in postmenopausal patients with RA receiving oral BP.Methods: This retrospective longitudinal observational study comprised 98 postmenopausal RA patients receiving oral BP for a minimum of 6 months between April 2015 and December 2020. The cumulative incidence of fragility fractures including vertebral and nonvertebral fractures was investigated using the Kaplan–Meier method. Cox proportional hazards analysis was used to analyze baseline predictors of future fragility fractures. To determine a cutoff value of continuous predictors, the receiver-operating characteristic curve was applied.Results: Twenty patients developed fractures during the study period, with a cumulative incidence of 6.1% at 12 months, 10.5% at a median follow-up of 28 months, and 14.4% at 36 months. Multivariable Cox hazards analysis showed a history of prior vertebral fracture (hazard ratio [HR]: 6.26, 95% confidence interval [CI]: 1.99‒19.68, P = 0.001) and dose of methotrexate (HR: 0.87, 95% CI: 0.76‒0.99, P = 0.041) to be independent predictors. The cutoff value for methotrexate dose was 4 mg/week.Conclusions: We found a cumulative incidence of any fractures of 10.5% at 28 months in patients with RA currently being treated with oral BP. A history of prior vertebral fractures and methotrexate dose were positive and negative predictors for fractures, respectively. Practitioners should consider selecting another anti-osteoporotic drug in patients with RA who remain at risk despite receiving oral BP.

Anxiety Levels Predict Bone Mineral Density in Postmenopausal Women Undergoing Oral Bisphosphonates: A Two-Year Follow-Up

Clinical psychological factors may predict medical diseases. Anxiety level has been associated with osteoporosis, but its role on bone mineral density (BMD) change is still unknown. This study aimed to investigate the association between anxiety levels and both adherence and treatment response to oral bisphosphonates (BPs) in postmenopausal osteoporosis. BMD and anxiety levels were evaluated trough dual-energy X-ray absorptiometry and the Hamilton Anxiety Rating Scale (HAM-A), respectively. Participants received weekly medication with alendronate or risedronate and were grouped according to the HAM-A scores into tertiles (HAM-A 3 > HAM-A 2 > HAM-A 1). After 24 months, BMD changes were different among the HAM-A tertiles. The median lumbar BMD change was significantly greater in both the HAM-A 2 and HAM-A 3 in comparison with the HAM-A 1. The same trend was observed for femoral BMD change. Adherence to BPs was >75% in 68% of patients in the HAM-A 1, 79% of patients in the HAM-A 2, and 89% of patients in the HAM-A 3 (p = 0.0014). After correcting for age, body mass index, depressive symptoms, and the 10-yr. probability of osteoporotic fractures, anxiety levels independently predicted lumbar BMD change (β = 0.3417, SE 0.145, p = 0.02). In conclusion, women with higher anxiety levels reported greater BMD improvement, highlighting that anxiety was associated with adherence and response to osteoporosis medical treatment, although further research on this topic is needed.

DENTAL IMPLANTS IN MEDICALLY COMPROMISED PATIENTS

The present study was carried out with an aim and interest to evaluate the status of implant, its function, and durability which are placed in the medically compromised patient .The literature review was done in order to identify the medically compromised patients with implants and were on medication with oral bisphosphonates for the ossication to be formed around dental implants for its vital function. The articles published between the years2001 to 2010 were included in the study. The articles of clinical studies in which 7-8 patients were treated, consensus articles,review articles and meta analysis were included. The total of 34 articles was found in which 26 articles met the inclusion criteria. The systematic diseases/ medically compromised are those patients with cardiac, diabetic,endocrine disorders and who are also seems to treated with dental implant and its outcomes.

Factors Associated With Inadequate Response to Bisphosphonate Therapy in Patients With Osteoporosis in Real-Life Clinical Practice: a Single-Center Retrospective Analysis of 300 Patients

Introduction: Bone mineral density (BMD) measurement by dual X-ray absorptiometry (DXA) is a useful tool to monitor response to osteoporosis treatment in clinical practice. Despite bisphosphonates therapy, some patients may exhibit bone loss during treatment for different reasons. These patients may have greater fracture risk than responders and may have unrecognized secondary causes that require further attention and treatment. Objectives: To identify factors associated with inadequate response (IR) to bisphosphonates therapy in patients with osteoporosis in real-life clinical practice. Methods: This is a single-center case-control study of patients with osteoporosis treated with bisphosphonates as recommended. Baseline and follow-up (12–24 months/apart) DXA scans were performed on same device (GE-Lunar Prodigy). IR was defined as loss of BMD greater than the least significant change (LSC) on the follow-up DXA. Clinical, biochemical and densitometric parameters of patients with IR were compared to responders using t-test or Mann-Whitney test (continuous), or chi-square test (categorical variables), as appropriated. We used logistic regression to assess the association magnitude between exposures and IR. Results: From 300 patients included from 2014 to 2018 (13% males, mean age 68 ±10 years), 198(66%) were treated with oral bisphosphonates and 102(34%) with zoledronic acid (ZA). IR was observed in 44(15%) patients. All parameters were similar at baseline, except for greater prevalence of oral bisphosphonates (82% vs 63%, p=0.016) and anticonvulsants use (18% vs 7%, p=0.015) in patients with IR compared to responders. Additionally, patients with IR exhibited a lower % change in CTX following therapy in comparison to responders (median -37% [IQR -68; -16%] vs -57% [-74; -32], p=0.029, respectively), and higher serum CTX levels after treatment (median 236pg/mL [IQR 162; 344] vs 165pg/mL [119; 254], p=0.004). The likelihood of IR was greater with oral bisphosphonates then with ZA (OR 2.61, IC95% 1.16–5.81, p=0.002), and with anticonvulsants use (OR 2.94. IC95% 1.19–7.25, p=0.019). The association with IR persisted for both variables (p≤0.01), when accounted simultaneously in the same model, along with age and gender. Conclusion: Inadequate bisphosphonate response was present in 15% of individuals, which was independently associated with anticonvulsant use and particularly among those on oral bisphosphonate therapy rather than ZA. This knowledge may help to clinically identify potential modifiable factors related to unresponsiveness and to optimize treatment accordingly.

Persistence with oral bisphosphonates and denosumab among older adults in primary care in Ireland

Summary Gaps in pharmacological treatment for osteoporosis can reduce effectiveness. Among older adults, we found about half of new users of oral bisphosphonate and denosumab persisted with their treatment at 2 years, with few switching to alternative therapy. Persistence is suboptimal and warrants evaluation of interventions to improve this. Purpose Gaps in pharmacological treatment for osteoporosis can reduce effectiveness. This study aimed to estimate persistence rates for oral bisphosphonates and denosumab in older primary care patients and identify factors associated with discontinuation. Methods Older patients newly prescribed oral bisphosphonates or denosumab during 2012–2017 were identified from 44 general practices (GP) in Ireland. Persistence without a coverage gap of >90 days was calculated for both medications from therapy initiation. Factors associated with time to discontinuation were explored using Cox regression analysis. Exposures included age group, osteoporosis diagnosis, fracture history, calcium/vitamin D prescription, number of other medications, health cover, dosing frequency (bisphosphonates) and previous bone-health medication (denosumab). Results Of 41,901 patients, n=1569 were newly initiated on oral bisphosphonates and n=1615 on denosumab. Two-year persistence was 49.4% for oral bisphosphonates and 53.8% for denosumab and <10% were switched to other medication. Having state-funded health cover was associated with a lower hazard of discontinuation for both oral bisphosphonates (HR=0.49, 95% CI=0.36–0.66, p<0.01) and denosumab (HR=0.71, 95% CI=0.57–0.89, p<0.01). Older age group, number of medications and calcium/vitamin D prescription were also associated with better bisphosphonate persistence, while having osteoporosis diagnosed was associated with better denosumab persistence. Conclusion Persistence for osteoporosis medications is suboptimal. Of concern, few patients are switched to other bone-health treatments when denosumab is stopped which could increase fracture risk. Free access to GP services and medications may have resulted in better medication persistence in this cohort. Future research should explore prescribing choices in primary care osteoporosis management and evaluate cost-effectiveness of interventions for improving persistence.

Optimal Dosing Regimen of Osteoporosis Drugs in Relation to Food Intake as the Key for the Enhancement of the Treatment Effectiveness—A Concise Literature Review

Bisphosphonates and selective estrogen receptor modulators (SERMs) represent the two most important groups of medications taken orally and employed in osteoporosis treatment. Effectiveness of the therapy may be affected by poor patient adherence, in particular, due to the inconvenient dosing regimen of oral bisphosphonates. With this review we aimed to assess the effects that food, beverages, and dietary supplements consumed during treatment, along with the dosing regimens, may have on pharmacokinetics and pharmacodynamics of oral drugs employed in treating osteoporosis; we also aimed to shape the recommendations valuable for professional patients’ counseling and education, to provide appropriate dosing regimens in order to improve adherence to the therapy. Food, beverages such as coffee, juices, and mineral water, as well as dietary supplements containing multivalent cations, e.g., calcium, magnesium, aluminium, iron, showed to have a deleterious effect on the bioavailability of all the investigated oral bisphosphonates, specifically alendronate, risedronate, ibandronate, minodronate, and etidronate. For risedronate, a delayed-release (DR) tablet was designed to solve the malabsorption problem in the presence of food, hence DR risedronate can be ingested following breakfast. For other oral bisphosphonates, the proper interval between drug and food, beverages, and dietary supplements intake should be maintained to minimize the risk of interactions. The effect of food on pharmacokinetic parameters of selective estrogen receptor modulators (SERMs) was found to be clinically irrelevant.

A Clinical and Histological Study about the Socket Preservation in a Patient under Oral Bisphosphonates Treatment: A Case Report

The aim of the present study is to assess the clinical and histological healing of a post-extractive alveolus following the procedure for socket preservation, in a patient receiving oral bisphosphonates for more than 6 years. After the extraction, enzymatically-deantigenated horse bone granules and an equine pericardium membrane were used to preserve the tooth socket. The patient was placed on a monthly follow-up in order to monitor the healing process. A 3 mm trephine bur was used to drill the bone for implant site preparation and to collect the bone sample. No signs and symptoms related to osteonecrosis of the jaws were reported. Histological data showed that, after 5 months, the mean percentages of trabecular bone, bone marrow and residual bone graft were respectively 45.74 ± 0.09%, 48.09 ± 0.08%, and 6.16 ± 0.01%. The residual graft material appeared to be osteointegrated and none of the particles appeared to be encapsulated. The present case report supports the guidelines that assume that patients undergoing oral bisphosphonate therapy can be eligible for surgical therapy. More clinical studies with larger sample sizes are needed to support this clinical evidence.