Oral Bisphosphonate Use Research Articles

Effect of Oral Bisphosphonate Drug Holiday on Mortality Following Hip Fracture.

Current clinical guidelines recommend a drug holiday after extended use of oral bisphosphonates. However, no studies have investigated the effect of drug holidays before hip fractures on postfracture mortality. This work aimed to investigate the effect of a drug holiday on postfracture mortality in patients with extended use of oral bisphosphonates. This retrospective, population-based cohort study took place among all patients with hip fractures in Victoria, Australia, from 2014 to 2018. Patients were adherent to oral alendronate or risedronate for 5 years or more prior to hip fracture. Group-based trajectory modeling categorized patients into different bisphosphonate usage after 5-year good adherence. The main outcome measure was postfracture mortality. We identified 365 patients with good adherence (medication possession ratio ≥80%) to oral alendronate/risedronate for 5 years or more. Most patients (69%) continued to use oral bisphosphonates until admission for hip fracture; 17% had discontinued for 1 year and 14% had discontinued for 2 years. Postfracture mortality was higher in patients who had discontinued risedronate for 1 year (hazard ratio [HR] 2.37; 95% CI, 1.24-4.53) and 2 years (HR 3.08; 95% CI, 1.48-6.41) prior to hip fracture. No increase or decrease in postfracture mortality was observed in patients who had discontinued alendronate for 1 year (HR 0.59; 95% CI, 0.29-1.18) or 2 years (HR 1.05; 95% CI, 0.57-1.93) prior to hip fracture. Postfracture mortality is higher in people who discontinue risedronate, but not alendronate, for 1 or 2 years after being adherent to treatment for at least 5 years. The type of bisphosphonate may be a factor to consider when planning drug holidays.

Patient preference, efficacy, and compliance with zoledronic acid for glucocorticoid-induced osteoporosis in patients with autoimmune diseases.

We evaluated the preference, patient satisfaction, and efficacy of zoledronic acid compared with oral bisphosphonates (BPs) for glucocorticoid-induced osteoporosis (GIOP) in patients with autoimmune diseases. We enrolled 50 patients with new fractures or osteoporosis detected on follow-up bone densitometry after at least 1year of oral BP use among patients diagnosed with GIOP during treatment for autoimmune diseases. After 1year of zoledronic acid treatment, patients completed a survey for preference and satisfaction assessment. Treatment efficacy was analysed by comparing bone mineral density changes and fractures with those in a control group of patients who continued oral BP use. Age, sex, treatment duration, and medication history did not differ significantly between the two groups. Among the participants, 86.7% preferred and were more satisfied with intravenous zoledronic acid than with oral BPs, primarily because of the convenience of its administration interval. Only two patients (4%) reported infusion-related adverse events with zoledronic acid. Furthermore, no significant differences were observed in the annualized percentage change in the bone mineral density of the lumbar spine, femur neck, and hip between patients receiving zoledronic acid and those receiving oral BPs. The occurrence of new fractures was consistent across both groups, with two cases in each, showing no significant differences. Patients showed a preference for and greater satisfaction with zoledronic acid, and its efficacy in treating osteoporosis was comparable to that of oral BPs. Therefore, zoledronic acid is a suitable treatment option for GIOP in patients with autoimmune diseases.

Trajectories of oral bisphosphonate use after hip fractures: a population-based cohort study

SummaryBisphosphonates prevent future hip fractures. However, we found that one in six patients with hip fractures had a delay in bisphosphonate initiation and another one-sixth discontinued treatment within 12 months after discharge. Our results highlight the need to address hesitancy in treatment initiation and continuous monitoring.PurposeSuboptimal antiresorptive use is not well understood. This study investigated trajectories of oral bisphosphonate use following first hip fractures and factors associated with different adherence and persistence trajectories.MethodsWe conducted a retrospective study of all patients aged ≥ 50 years dispensed two or more bisphosphonate prescriptions following first hip fracture in Victoria, Australia, from 2012 to 2017. Twelve-month trajectories of bisphosphonate use were categorized using group-based trajectory modeling. Factors associated with different trajectories compared to the persistent adherence trajectory were assessed using multivariate multinomial logistic regression.ResultsWe identified four patterns of oral bisphosphonate use in 1811 patients: persistent adherence (66%); delayed dispensing (17%); early discontinuation (9%); and late discontinuation (9%). Pre-admission bisphosphonate use was associated with a lower risk of delayed dispensing in both sexes (relative risk [RR] 0.28, 95% confidence interval [CI] 0.21–0.39). Older patients (≥\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\ge$$\\end{document} 85 years old versus 50–64 years old, RR 0.38, 95% CI 0.22–0.64) had a lower risk of delayed dispensing. Males with anxiety (RR 9.80, 95% CI 2.24–42.9) and females with previous falls had increased risk of early discontinuation (RR 1.80, 95% CI 1.16–2.78).ConclusionTwo-thirds of patients demonstrated good adherence to oral bisphosphonates over 12 months following hip fracture. Efforts to further increase post-discharge antiresorptive use should be sex-specific and address possible persistent uncertainty around delaying treatment initiation.

Low screening rates and high prevalence of osteoporosis in cirrhosis: A real-world retrospective analysis.

Patients with cirrhosis are at increased risk for osteoporosis, and those who suffer a fracture are at high risk for mortality. Despite this, osteoporosis is often overlooked and undertreated. This study aimed to evaluate osteoporosis screening, management, and adverse osteoporosis medication events in patients with cirrhosis. We performed a retrospective chart review of adult outpatients with compensated and decompensated cirrhosis seen in single health system over a 6-year period. Patient demographics, liver and bone health comorbidities, DEXA scan results, and medications were abstracted. In total, 5398 patients met criteria. The cohort was predominately white (79.1%) and older (age 59). 44.4% were female. 64.6% had decompensated cirrhosis. Median MELD-Na score was 12.8. 23.5% had a DEXA scan ordered, approximately 50% completed this test. Patients who were older, female, white, with more severe liver disease, and other osteoporosis risk factors were more likely to have a DEXA scan ordered. 48.5% of patients had osteopenia and 30.2% had osteoporosis on DEXA scan. Only 22.6% of patients with osteoporosis received treatment, most commonly oral bisphosphonates. Oral bisphosphonate prescription was not associated with variceal bleeding (8.4% without vs. 4.8% with, p = 0.487). A minority of patients with cirrhosis were screened for osteoporosis. The majority screened had osteopenia or osteoporosis on DEXA scan. Less than a quarter of patients with osteoporosis were started on treatment. Real-world experience of oral bisphosphonate use did not reveal higher rates of gastrointestinal bleeding. There is room for improvement in all aspects of bone health care in cirrhosis.

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

Endocrinology for the hepatologist.

Endocrinology for the hepatologist.

Zoledronate and osteonecrosis of the jaw in osteoporosis: incidence and risk factors. Analysis of the French Pharmacovigilance Database

IntroductionBisphosphonate-related osteonecrosis of the jaw (BRONJ) have been characterized with the use of oral bisphosphonates in osteoporosis and zoledronate in oncology. Uncertainties remain, though, with the occurrence of BRONJ related to the use of zoledronate in osteoporosis. ObjectivesWe aimed to estimate the incidence and characterize the risk factors of zoledronate-associated BRONJ in osteoporosis as compared with oral bisphosphonates in real life setting. MethodsCases of BRONJ associated with zoledronate, alendronate or risedronate were extracted from the French pharmacovigilance database up to 2020. The incidence of BRONJ was estimated as their respective numbers related to cases of BRONJ in patients treated with bisphosphonates for osteoporosis, over the same period, according to the Medic’AM database. ResultsBetween 2011 and 2020, BRONJ incidence with zoledronate was 9.6/100,000 patient-year (PY), significantly higher than with alendronate (5.1/100,000 PY, P<0.001), and risedronate (2.0/100,000 PY, P<0.001). The number of patients treated with bisphosphonates has steadily decreased by 44.5% over 10 years. Meanwhile, the incidence of BRONJ decreased (5.8/100,000 PY in 2011; 1.5/100,000 in 2020), although a rebound was observed in 2018, including 47.6% of BRONJ following denosumab. Apart from classical risk factors, recent dental cares stood out in more than 40% of BRONJ, and zoledronate had a shorter exposure time than oral bisphosphonates. ConclusionsIn a real-life setting, our data confirm that zoledronate-associated BRONJ in osteoporosis is scarce, seeming slightly more common compared with oral bisphosphonates. We also raise awareness of dental care guidelines and greater vigilance when using bisphosphonates in patients with previous exposure to denosumab.

Association of oral bisphosphonates with cardioembolic ischemic stroke: a nested case-control study.

Background: Bisphosphonates have been reported to increase the risk of atrial fibrillation. Therefore, it is conceivable that they may increase the risk of cardioembolic ischemic stroke (IS). However, most epidemiological studies carried out thus far have not shown an increased risk of IS, though none separated by the main pathophysiologic IS subtype (cardioembolic and non-cardioembolic) which may be crucial. In this study, we tested the hypothesis that the use of oral bisphosphonates increases specifically the risk of cardioembolic IS, and explored the effect of treatment duration, as well as the potential interaction between oral bisphosphonates and calcium supplements and anticoagulants. Methods: We performed a case-control study nested in a cohort of patients aged 40-99years, using the Spanish primary healthcare database BIFAP, over the period 2002-2015. Incident cases of IS were identified and classified as cardioembolic or non-cardioembolic. Five controls per case were randomly selected, matched for age, sex, and index date (first recording of IS) using an incidence-density sampling. The association of IS (overall and by subtype) with the use of oral bisphosphonates within the last year before index date was assessed by computing the adjusted odds ratios (AOR) and their 95% CI using a conditional logistic regression. Only initiators of oral bisphosphonates were considered. Results: A total of 13,781 incident cases of IS and 65,909 controls were included. The mean age was 74.5 (SD ± 12.4) years and 51.6% were male. Among cases, 3.15% were current users of oral bisphosphonates, while among controls they were 2.62%, yielding an AOR of 1.15 (95% CI:1.01-1.30). Of all cases, 4,568 (33.1%) were classified as cardioembolic IS (matched with 21,697 controls) and 9,213 (66.9%) as non-cardioembolic IS (matched with 44,212 controls) yielding an AOR of 1.35 (95% CI:1.10-1.66) and 1.03 (95% CI: 0.88-1.21), respectively. The association with cardioembolic IS was clearly duration-dependent (AOR≤1year = 1.10; 95% CI:0.82-1.49; AOR>1-3years = 1.41; 95% CI:1.01-1.97; AOR>3years = 1.81; 95% CI:1.25-2.62; p for trend = 0.001) and completely blunted by anticoagulants, even in long-term users (AOR>1year = 0.59; 0.30-1.16). An interaction between oral bisphosphonates and calcium supplements was suggested. Conclusion: The use of oral bisphosphonates increases specifically the odds of cardioembolic IS, in a duration-dependent manner, while leaves materially unaffected the odds of non-cardioembolic IS.

Denosumab and incidence of type 2 diabetes among adults with osteoporosis: population based cohort study

ObjectiveTo estimate the effect of denosumab compared with oral bisphosphonates on reducing the risk of type 2 diabetes in adults with osteoporosis.DesignPopulation based study involving emulation of a randomized target...

Investigation of the effect of oral and internal bisphosphonate use on bone density in the jaws in patients with osteoporosis in panoramic radiography

This study aims to quantitatively evaluate the effects of bisphosphonate use duration and route of administration on mandibular cortical and trabecular bone in postmenopausal women. Ninety postmenopausal women over the age of 50 were included in this study. Trabecular bone density was specified numerically by fractal dimension (FD) in the region of interest selected on the panoramic radiograph. The width of the mandibular cortical (MCW) bone under the mental foramen of the mandible was measured. Mann-Whitney U test was used for parameters that did not show a normal distribution. Spearman rho correlation test was used to determine the relationship between continuous measurement parameters. It was observed that FD and MCW of dentate and edentate individuals using bisphosphonate were statistically significantly lower than those of healthy individuals (P < .05). There was no significant correlation was found between the duration of use of bisphosphonates and the fractal values obtained from the relevant regions of the mandible (P > .05). Fractal dimension was found to be lower in oral bisphosphonate use than in intravenous bisphosphonate use. The width of the mandibular cortical bone values was found to be lower in individuals using bisphosphonate than in healthy individuals. Fractal dimension and MCW may benefit clinicians as quantitative parameters in panoramic radiography in the diagnosis of osteoporosis.

Treatment of Apical Periodontitis Induced BRONJ with Endodontic Treatment

Bisphosphonate-related osteonecrosis of the jaw (BRONJ), which is one of the serious side effects of bisphosphonates, has an increasing clinical importance due to the widespread use of bisphosphonates in the treatment of many diseases such as osteoporosis, osteopenia, Paget's disease, osteogenesis imperfecta, and multiple myeloma. BRONJ can spontaneously develop in the jawbones. In addition, many factors such as tooth extraction, periodontal diseases, and local trauma can trigger BRONJ. In our case, it was detected that the lesion appearing like BRONJ in the left lower jaw of the 67-year-old female patient with a history of oral bisphosphonate use developed due to apical periodontitis resulting from the tooth numbered 34. Root canal treatment was administered to the relevant tooth of the patient, the fistula tract was closed after this treatment, and as a result of the CBCT examination, it was observed that the enlargement in the necrotic bone area stopped. In addition, the patient's complaints about the relevant tooth disappeared. As a result, endodontic treatment is an effective treatment approach in the treatment of BRONJ developing due to apical periodontitis. In order to avoid the risk of BRONJ, a detailed oral examination should be performed before starting the bisphosphonate treatment, and necessary endodontic, restorative and periodontal treatments should be followed.

ODP107 Oral Ulcerations, A Rare Side Effect of Intravenous Zoledronic Acid

Abstract Introduction Zoledronic acid is an intravenous bisphosphonate known for its anti-resorptive effects and osteoporotic fracture risk reduction. A common adverse reaction with this medication is mild to moderate flu-like symptoms, which are transient and attributed to an acute phase reaction post treatment. A less common side effect, of oral ulcers is associated with oral bisphosphonates, attributed to incorrect oral intake but the real mechanism is still not well understood. We present a patient that developed oral ulcers after use of both oral and intravenous bisphosphonates, leading to suspicion of other underlying mechanisms other than incorrect oral intake of bisphosphonates. Case Report We present a 73 year old male with history of mild primary hyperparathyroidism and osteoporosis. Patient opted for medical management of his mild primary hyperparathyroidism in addition to having non-localizing studies. Treatment for osteoporosis was recommended due to femoral neck T score -2.4, FRAX score of 3.3% risk for hip fractures and history of low impact right foot fracture. The primary care team started treatment with alendronate 70 mg once a week, but patient developed oral blisters within a week of starting the treatment. Stopping alendronate led to resolution of the oral symptoms without any additional supportive treatment. Patient was later started on intravenous zoledronic acid, attributing the previous history of oral ulcers to a local effect of the oral bisphosphonates. Two days after the zoledronic acid infusion patient developed fatigue, fever, and oral ulcers. The oral ulcers were described as painful, located at the base and lateral aspects of the tongue. The ulcers later progressed to the buccal mucosa. No gingival ulcers were reported. Development of the oral blisters led to significant discomfort in eating and talking. Patient was treated with liquid nystatin 10,000 units/mL and lidocaine 2% viscous liquid. Patient had resolution of the painful ulcers approximately 2 weeks after the initial appearance. No recurrence of the oral ulcers has been reported, 4 months post treatment with zoledronic acid. Discussion Intuitively oral bisphosphonate induced mucosal injury is thought to be related to direct contact of the tablet with the oral mucosa or inappropriate ingestion of the medication and is not thought to be a systemic reaction. Our patient developed oral ulcers from both oral and intravenous bisphosphonates suggesting a possible systemic mechanism involved. Understanding potential side effects such as mucosal injury from intravenous bisphosphonates will be helpful for patient education and timely care. Presentation: No date and time listed

Trabecular bone microcrack accumulation in patients treated with bisphosphonates for durations up to 16 years.

This study quantified the length, number, and density of microcracks in bone from patients treated with bisphosphonates as a function of duration. Anterior iliac crest bone samples from 51 osteoporotic Caucasian females continuously treated with oral bisphosphonates for 1-16 years were obtained by bone biopsy. Samples were histologically processed and analyzed for bone area, microcrack number, and microcrack length. The analyses used statistical modeling and considered patient age, bone mineral density, bone volume/total volume, trabecular thickness, and bone turnover as potential covariates. Microcrack density (number of microcracks/total examined bone area) was linearly related (p = 0.018) to bisphosphonate treatment duration. None of the analyzed covariates contributed significantly to the observed relationship between microcrack density and bisphosphonate treatment duration. Observed increases in microcrack density with increasing bisphosphonate treatment duration is important because increasing levels of microcracks may not only affect bone remodeling but also reduce elastic modulus and are suspected to adversely affect other mechanical properties that may influence fracture risk. The present findings add to our prior results showing changes in bone material properties and modulus with bisphosphonate treatment duration and thereby provide a more comprehensive assessment of the relationship between bisphosphonate treatment duration and bone quality. Statement of Clinical Significance: The present findings provide information guiding clinical use of oral bisphosphonates for post-menopausal osteoporosis therapy.

EXTENSIVE EXPERTISE IN ENDOCRINOLOGY: Osteoporosis management.

Fractures occur in about half of older White women, and almost a third of older White men. However, 80% of the older individuals who have fractures do not meet the bone density definition of osteoporosis, suggesting that this definition is not an appropriate threshold for offering treatment. Fracture risk can be estimated based on clinical risk factors with or without bone density. A combination of calculated risk, fracture history, and bone density is used in treatment decisions. Medications available for reducing fracture risk act either to inhibit bone resorption or to promote bone formation. Romosozumab is unique in that it has both activities. Bisphosphonates are the most widely used interventions because of their efficacy, safety, and low cost. Continuous use of oral bisphosphonates for >5 years increases the risk of atypical femoral fractures, so is usually punctuated with drug holidays of 6-24 months. Denosumab is a further potent anti-resorptive agent given as 6-monthly s.c. injections. It is comparable to the bisphosphonates in efficacy and safety but has a rapid offset of effect after discontinuation so must be followed by an alternative drug, usually a bisphosphonate. Teriparatide stimulates both bone formation and resorption, substantially increases spine density, and reduces vertebral and non-vertebral fracture rates, though data for hip fractures are scant. Treatment is usually limited to 18-24 months, followed by the transition to an anti-resorptive. Romosozumab is given as monthly s.c. injections for 1 year, followed by an anti-resorptive. This sequence prevents more fractures than anti-resorptive therapy alone. Because of cost, anabolic drugs are usually reserved for those at very high fracture risk. 25-hydroxyvitamin D levels should be maintained above 30 nmol/L, using supplements if sunlight exposure is limited. Calcium intake has little effect on bone density and fracture risk but should be maintained above 500 mg/day using dietary sources.

The ocular findings related to oral bisphosphonate use

ObjectiveWe aimed to investigate ocular involvement findings in female osteoporosis patients using oral bisphosphonate (BP). MethodsA total of 51 female osteoporosis patients aged 50–75 years using oral BP for at least one year for the study group and 64 age-matched non-osteoporosis female patients for the control group were included in the study. The BP type and exposure time were noted. The ophthalmic examination findings and measurements of the flare of the patients who received oral BP due to osteoporosis and the controls were evaluated. ResultsThe mean duration of BP use was 3.96 years. In the study group, it was detected four of 51 patients were diagnosed with meibomian gland dysfunction (MGD) (7.8%), seven of 102 eyes had erythematous, irregular, thickened lid margin or telangiectasia around the glandular orifices. There were no pathological findings on fundus examination. The mean value of measurements of the flare (ph/ms) was 7.90±7.96 in the study group, and 5.02±0.81 in the control group. When the mean values were compared, there was a significant difference between the two groups (P=.001). A significant difference was found in the mean value of measurements of the flare between the patients using alendronate, and ibandronate with the control group (P=.001; P=.005, respectively). ConclusionOur study showed that the flare in the anterior chamber associated with chronic ocular inflammation can be seen higher rate in patients using oral alendronate, and ibandronate compared to those who do not. Morever it can be said that oral BPs may cause similar ocular side effects like as intravascular BPs.

Incident peptic ulcers and concomitant treatment of direct oral anticoagulants and oral bisphosphonates-a real-world cohort study.

This study examines whether concomitant use of oral bisphosphonates (oBP) and direct oral anticoagulants (DOAC) increases the risk of peptic ulcers more than any drug alone. A population-based cohort study was performed. We sampled a cohort of oBP and DOAC users from a sample of 2,622,742 individuals, consisting of diabetes patients and age- and gender-matched controls, obtained from the Danish National Patient Register. The exposures were concomitant use of oBP and DOAC and single use of DOAC and single use of oBP. The primary endpoint was the first incident peptic ulcer. Information on exposure and outcome were collected from national registries. The period of observation was from 01.01.2008 until 31.12.2018. Unadjusted and adjusted Cox regressions were performed. 8077 individuals received concomitant treatment with DOAC and oBP; 96,451 individuals used DOAC and no oBP; and 118,675 used oBP and no DOAC. The mean duration of follow-up was 1.9years for concomitant users, 2.5years for DOAC users, and 4.5years for oBP users. A total of 4742 individuals with incident peptic ulcers were collected. We observed an increased risk of incident ulcer in users of DOAC and oBP compared to single DOAC treatment in the adjusted analysis (HR = 1.23, 95% CI: 1.03; 1.48). However, the effects were abolished when excluding individuals with a previous ulcer. We observed an increased risk of incident ulcer in users of DOAC and oBP compared to users of oBP in the adjusted model (HR = 1.34, 95% CI: 1.11; 1.63). Based on our results, concomitant use of oBP and DOAC is associated with a slight increase in the risk of peptic ulcers compared to either drug alone. The prescribing physician should weigh the slight increased risk of ulcer in concomitant users of oBP and DOAC with beneficial reductions in stroke and fractures.

Indications for initiation of drug therapy and modern therapy protocols in patients with osteoporosis

Introduction. Pharmacotherapy and physical therapy in patients with osteoporosis are aimed at increasing bone density and reducing the risk of fall in order to prevent fractures. Medications approved for the treatment of osteoporosis reduce the risk of fracture, either by reducing bone resorption or by stimulating bone formation. Bisphosphonates are most widely used antiresorptive agents that lower bone turnover markers to premenopausal levels and reduce fracture rates. Bisphosphonates bind to bone minerals and have a long-lasting effect. Long-term, continuous use of oral bisphosphonates is usually interspersed with drug breaks of 1-2 years to reduce the risk of atypical femoral fractures. Denosumab is a monoclonal antibody that also acts as an antiresorptive and it targets receptor activators of nuclear factor-?B ligand thus inhibiting the formation and function of osteoclasts. Denosumab is administered as a subcutaneous injection every 6 months. Anti-fracture effects of denosumab are similar to those of bisphosphonates, but there is a marked loss of antiresorptive effect 7 months after the last dose, which may lead to recurrent vertebral fractures. Anabolic drugs work by stimulating bone formation. Teriparatide and abaloparatide bind to the parathyroid hormone-1 receptor and are given as daily subcutaneous injection for up to 2 years. Romosozumab is a monoclonal antibody that targets sclerostin, stimulates bone formation and inhibits resorption. The effects of anabolics are transient, so it is necessary to switch to antiresorptive medications. Conclusion. It is a matter of great importance to determine the optimal strategy for cycles of anabolics, antiresorptive drugs and therapy-free periods.

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.

Characteristics Associated with Acute-Phase Response following First Zoledronic Acid Infusion in Brazilian Population with Osteoporosis.

We aimed to evaluate characteristics associated with acute-phase response (APR) following first zoledronic acid infusion in a Brazilian cohort. This retrospective cohort study enrolled all adults with osteoporosis who underwent a first zoledronic acid infusion at our centre between June 2015 and June 2019. Clinical demographics (age, sex, diabetes, smoking, body mass index, and previous oral bisphosphonate use) and laboratory data (calcium, parathyroid hormone, renal function, and serum 25-hydroxyvitamin D and carboxy-terminal crosslinked telopeptide of type 1 collagen [CTX], both before and after infusion) were compared between patients with and without APR. We evaluated association magnitude between the presence of APR and clinical variables through logistic regression. This study enrolled 400 patients (women, 80%). APR was observed in 24.5% (n = 98) of patients. The mean symptom duration in days was 3.5 ± 2.8. Patients with APR were younger (67 ± 12 vs. 71 ± 11 years; p=0.001), used oral bisphosphonates less frequently (34% × 50%; p=0.005), and had greater baseline CTX (0.535 ng/mL [0.375, 0.697] × 0.430 [0.249, 0.681]; p=0.03) and ΔCTX (−69 [−76; −50] × −54 [−72; −23]; p=0.002) than those without APR. The other variables were similar between the groups. Only ΔCTX was associated (OR, 0.62; 95% CI 0.41–0.98) with APR after accounting for age and bisphosphonate use. APR occurred in 24.5% of the cohort. Younger age and absence of prior oral bisphosphonate use were associated with APR following first zoledronic acid infusion. APR was associated with ΔCTX (but no other variables) after adjusting for these factors.

One- and 2-year incidence of osteoporotic fracture: a multi-cohort observational study using routinely collected real-world data

SummaryWe estimated and characterized the imminent fracture risk (1–2 years) of high-risk fracture patients through a multinational (UK, Spain, Denmark) cohort study. Older individuals with newly diagnosed osteoporosis and individuals who had a fracture while on treatment with a bisphosphonate were at a high risk of imminent fracture.PurposeTo characterize and estimate 1- to 2-year fracture risk in high-risk fracture patients.MethodsMulti-cohort study in (database/study period) UK (CPRD/1995–2017), Spain (SIDIAP/2006–2016) and Denmark (DHR/1995–2016) including individuals ≥ 50 years old in NDO (newly diagnosed osteoporosis), OFx (incident osteoporotic fracture), BP (incident oral bisphosphonates use) or FWOT (fracture while on treatment with bisphosphonates). Outcomes (ICD-10/READ): hip, clinical spine, non-hip, non-spine and hip/humerus/distal forearm fracture. Follow-up: from cohort entry until death, migration/transfer or end of the study. Statistics: baseline characteristics and incidence rate (IR per 1000 persons).Results (1-year IR)NDO included 69,899 (UK), 37,901 (Spain) and 158,191 (Denmark) individuals. Spanish-IR was lowest for hip (4.7), clinical spine (2.5) and major osteoporotic fracture (MOF) (17.3) and highest in Denmark (74.2, 26.0 and 120.1, respectively). OFx included 83,514 (UK), 51,044 (Spain) and 509,551 (Denmark) individuals. IR in Denmark was highest for hip (24.1) and MOF (47.2), in Spain was highest for the clinical spine (9.4) and lowest for hip (9.5) and in the UK was lowest for the clinical spine (2.8) and MOF (20.7). BP included 148,507 (UK), 52,037 (Spain) and 204,010 (Denmark) individuals. Spanish-IR was lowest for hip (5.0) and MOF (21.1) and highest in Denmark (20.3 and 48.6, respectively). FWOT included 28,930 (UK), 1,865 (Spain) and 31,882 (Denmark) individuals. Clinical spine-IR was highest for Spain (12.0). Hip-IR was lowest for Spain (7.6) and highest for Denmark (33.6). Comparing young subjects, those who have FWOT started with an increased fracture rate.ConclusionOFx and FWOT individuals experience higher re-fracture incidence rates than those with osteoporosis with or without treatment.