Management of bone metastasis and cancer treatment-induced bone loss during the COVID-19 pandemic: An international perspective and recommendations.

Optimum management of patients with cancer during the COVID-19 pandemic has proved extremely challenging. Patients, clinicians and hospital authorities have had to balance the risks to patients of attending hospital, many of whom are especially vulnerable, with the risks of delaying or modifying cancer treatment. Those whose care has been significantly impacted include patients suffering from the effects of cancer on bone, where delivering the usual standard of care for bone support has often not been possible and clinicians have been forced to seek alternative options for adequate management. At a virtual meeting of the Cancer and Bone Society in July 2020, an expert group shared experiences and solutions to this challenge, following which a questionnaire was sent internationally to the symposium's participants, to explore the issues faced and solutions offered. 70 respondents, from 9 countries (majority USA, 39%, followed by UK, 19%) included 50 clinicians, spread across a diverse range of specialties (but with a high proportion, 64%, of medical oncologists) and 20 who classified themselves as non-clinical (solely lab-based). Spread of clinician specialty across tumour types was breast (65%), prostate (27%), followed by renal, myeloma and melanoma. Analysis showed that management of metastatic bone disease in all solid tumour types and myeloma, adjuvant bisphosphonate breast cancer therapy and cancer treatment induced bone loss, was substantially impacted. Respondents reported delays to routine CT scans (58%), standard bone scans (48%) and MRI scans (46%), though emergency scans were less affected. Delays in palliative radiotherapy for bone pain were reported by 31% of respondents with treatments often involving only a single dose without fractionation. Delays to, or cancellation of, prophylactic surgery for bone pain were reported by 35% of respondents. Access to treatments with intravenous bisphosphonates and subcutaneous denosumab was a major problem, mitigated by provision of drug administration at home or in a local clinic, reduced frequency of administration or switching to oral bisphosphonates taken at home. The questionnaire also revealed damaging delays or complete stopping of both clinical and laboratory research. In addition to an analysis of the questionnaire, this paper presents a rationale and recommendations for adaptation of the normal guidelines for protection of bone health during the pandemic.

Osteoporosis management in hematologic stem cell transplant recipients: Executive summary.

BACKGROUND: Treatment advances have reduced the adverse events associated with hematopoietic stem cell transplant (HSCT) and led to an increased number of transplants performed. HSCT patients are living longer with concerns on long-term outcomes. Bone fragility and fracture are at the forefront for long-term morbidities post-HSCT. RESULTS: In HSCT recipients, evidence has accumulated to support recommendations for more extensive monitoring of bone fragility and more appropriate administration of osteoporosis pharmacotherapies for patients at high risk of bone loss and/or fracture. CONCLUSION: This executive summary reports and summarizes the main recommendations published previously, including bone assessment, dietary and lifestyle recommendations and osteoporosis medication.

Influence of denosumab on bone mineral density in a severe case of pregnancy-associated osteoporosis.

Pregnancy and lactation-associated osteoporosis (PLO) with predominantly subsequent vertebral fracture is a rare but severe disease with an estimated incidence of 0.4 in 100,000. In the past, patients with PLO have been predominantly treated with oral and i.v. bisphosphonates to reduce subsequent fracture risk. Hereby, the use of bisphosphonates in premenopausal women is controversial, as bisphosphonates know to persist in bone for many years and can be exposed and circulate in maternal serum and subsequently pass the placenta barrier and may have a detrimental effect on fetal bone health. Here we report the effects of denosumab on the bone mineral density (BMD) and subsequent fracture risk in PLO. In this case presentation, denosumab was administered postpartum with 3000 IE vitamin D and 1000 mg of calcium daily in a patient with PLO and vertebral fracture of L1 and L4. After 18 months of treatment with denosumab, we could demonstrate a clinical significant increase of BMD at the lumbar spine, femoral neck, and total hip of 32.2%, 13.0%, and 11.5% respectively with no further subsequent fractures. As the patient had regular menstrual cycles and considered a further pregnancy, denosumab treatment was terminated and soon a second pregnancy occurred. After the second pregnancy, BMD decreased at the lumbar spine, femur neck, and total hip by -8.8%, -6.9%, and -7.0% respectively compared to the maximum values during treatment with denosumab, but was still significantly higher compared to baseline levels with no further fractures.

The osteoporosis treatment gap in patients at risk of fracture in European primary care: a multi-country cross-sectional observational study.

This study in 8 countries across Europe found that about 75% of elderly women seen in primary care who were at high risk of osteoporosis-related fractures were not receiving appropriate medication. Lack of osteoporosis diagnosis appeared to be an important contributing factor. INTRODUCTION: Treatment rates in osteoporosis are documented to be low. We wished to assess the osteoporosis treatment gap in women ≥ 70 years in routine primary care across Europe. METHODS: This cross-sectional observational study in 8 European countries collected data from women 70 years or older visiting their general practitioner. The primary outcome was treatment gap: the proportion who were not receiving any osteoporosis medication among those at increased risk of fragility fracture (using history of fracture, 10-year probability of fracture above country-specific Fracture Risk Assessment Tool [FRAX] thresholds, T-score ≤ - 2.5). RESULTS: Median 10-year probability of fracture (without bone mineral density [BMD]) for the 3798 enrolled patients was 7.2% (hip) and 16.6% (major osteoporotic). Overall, 2077 women (55%) met one or more definitions for increased risk of fragility fracture: 1200 had a prior fracture, 1814 exceeded the FRAX threshold, and 318 had a T-score ≤ - 2.5 (only 944 received a dual-energy x-ray absorptiometry [DXA] scan). In those at increased fracture risk, the median 10-year probability of hip and major osteoporotic fracture was 11.2% and 22.8%, vs 4.1% and 11.5% in those deemed not at risk. An osteoporosis diagnosis was recorded in 804 patients (21.2%); most (79.7%) of these were at increased fracture risk. The treatment gap was 74.6%, varying from 53% in Ireland to 91% in Germany. Patients with an osteoporosis diagnosis were found to have a lower treatment gap than those without a diagnosis, with an absolute reduction of 63%. CONCLUSIONS: There is a large treatment gap in women aged ≥ 70 years at increased risk of fragility fracture in routine primary care across Europe. The gap appears to be related to a low rate of osteoporosis diagnosis.

Effect of progestogen-only contraception on premenopausal fracture risk: a case-control study.

Our study demonstrated that progestogen-only oral and intrauterine contraceptives are not associated with fracture risk independent from age. PURPOSE: The use of progestogen-only contraception, resulting in a hypoestrogenic state, has been associated with impaired bone acquisition and increased fracture risk. The aim of this large population-based study was to assess the fracture risk in association with the use of progestogen-only contraceptives (progestogen-only pills (POPs) and progestogen-containing IUDs (LNG-IUD)). METHODS: We identified 14,421 women between 16 and 55 years of age with a first-time diagnosis of fracture and matched them with 14,421 random controls using the Disease Analyzer Database. RESULTS: The results of the first adjusted logistic regression model (ever use vs. never use of progestogen-only contraceptives) revealed that there was no significant association between the use of POPs (OR = 0.98, 95% CI 0.90-1.07, p = 0.657) or LNG-IUDs (OR = 0.99, 95% CI 0.81-1.21, p = 0.945) and fracture incidence. Also, in the second regression model, we observed no effect of duration of use of POPs (OR = 1.01, 95% CI 0.98-1.03, p = 0.672) or LNG-IUDs (OR = 0.94, 95% CI 0.87-1.02, p = 0.177) on fracture occurrence. We also observed no effect in different age groups. CONCLUSION: Our study results indicate that progestogen-only contraception (either POPs or LNG-IUPs) is not associated with fracture risk and may be considered a bone-safe option for adults and adolescents.

Incidence of fractures in patients with type 1 diabetes mellitus-a retrospective study with 4420 patients.

This retrospective study investigated the incidence of fracture in 4420 type 1 diabetes (T1DM) patients. Our findings indicate that patients with T1DM have an increased incidence of fractures. Further studies and preventive measures are urgently needed. INTRODUCTION: The aim of this study was to investigate the incidence of fracture in patients with type 1 diabetes mellitus (T1DM). METHODS: This study is based on the German Disease Analyzer database and included 4258 adult individuals with a T1DM diagnosis documented between January 2000 and December 2015 in 1203 general practices in Germany. Individual matching of T1DM and non-diabetic patients was performed. The cumulative incidence of new fractures was shown for up to 10 years after the index date using Kaplan-Meier curves. Cox proportional hazard models (dependent variable: incident fracture) were used to estimate the effect of T1DM on fracture incidence, as well as the effect of predefined variables on fracture incidence. RESULTS: After 10 years of follow-up, the cumulative fracture incidence was 18.4% for T1DM patients and 9.9% for non-diabetic patients (p < 0.001). A strong association between T1DM and fractures was found (HR, 2.01 (95% CI, 1.70-2.38) p < 0.001) in both female and male patients. Significant differences between T1DM and non-diabetes patients were found in lower leg/ankle, foot and toe, shoulder/upper arm, and rib(s), sternum and thoracic spine fractures. A significant association between higher age and fracture incidence was observed in T1DM patients. CONCLUSIONS: In summary, we found that patients with T1DM have a twofold increased fracture rate compared with healthy controls. Furthermore, fractures were associated with increased age and high HbA1c values.

Determinants, consequences and potential solutions to poor adherence to anti-osteoporosis treatment: results of an expert group meeting organized by the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) and the International Osteoporosis Foundation (IOF).

Many patients at increased risk of fractures do not take their medication appropriately, resulting in a substantial decrease in the benefits of drug therapy. Improving medication adherence is urgently needed but remains laborious, given the numerous and multidimensional reasons for non-adherence, suggesting the need for measurement-guided, multifactorial and individualized solutions. INTRODUCTION: Poor adherence to medications is a major challenge in the treatment of osteoporosis. This paper aimed to provide an overview of the consequences, determinants and potential solutions to poor adherence and persistence to osteoporosis medication. METHODS: A working group was organized by the European Society on Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal diseases (ESCEO) to review consequences, determinants and potential solutions to adherence and to make recommendations for practice and further research. A systematic literature review and a face-to-face experts meeting were undertaken. RESULTS: Medication non-adherence is associated with increased risk of fractures, leading to a substantial decrease in the clinical and economic benefits of drug therapy. Reasons for non-adherence are numerous and multidimensional for each patient, depending on the interplay of multiple factors, suggesting the need for multifactorial and individualized solutions. Few interventions have been shown to improve adherence or persistence to osteoporosis treatment. Promising actions include patient education with counselling, adherence monitoring with feedback and dose simplification including flexible dosing regimen. Recommendations for practice and further research were also provided. To adequately manage adherence, it is important to (1) understand the problem (initiation, implementation and/or persistence), (2) to measure adherence and (3) to identify the reason of non-adherence and fix it. CONCLUSION: These recommendations are intended for clinicians to manage adherence of their patients and to researchers and policy makers to design, facilitate and appropriately use adherence interventions.

Bone health in estrogen-free contraception.

Estrogens and progestogens influence the bone. The major physiological effect of estrogen is the inhibition of bone resorption whereas progestogens exert activity through binding to specific progesterone receptors. New estrogen-free contraceptive and its possible implication on bone turnover are discussed in this review. Insufficient bone acquisition during development and/or accelerated bone loss after attainment of peak bone mass (PBM) are 2 processes that may predispose to fragility fractures in later life. The relative importance of bone acquisition during growth versus bone loss during adulthood for fracture risk has been explored by examining the variability of areal bone mineral density (BMD) (aBMD) values in relation to age. Bone mass acquired at the end of the growth period appears to be more important than bone loss occurring during adult life. The major physiological effect of estrogen is the inhibition of bone resorption. When estrogen transcription possesses binds to the receptors, various genes are activated, and a variety modified. Interleukin 6 (IL-6) stimulates bone resorption, and estrogen blocks osteoblast synthesis of IL-6. Estrogen may also antagonize the IL-6 receptors. Additionally, estrogen inhibits bone resorption by inducing small but cumulative changes in multiple estrogen-dependent regulatory factors including TNF-α and the OPG/RANKL/RANK system. Review on existing data including information about new estrogen-free contraceptives. All progestins exert activity through binding to specific progesterone receptors; hereby, three different groups of progestins exist: pregnanes, gonanes, and estranges. Progestins also comprise specific glucocorticoid, androgen, or mineralocorticoid receptor interactions. Anabolic action of a progestogen may be affected via androgenic, anti-androgenic, or synadrogenic activity. The C 19 nortestosterone class of progestogens is known to bind with more affinity to androgen receptors than the C21 progestins. This article reviews the effect of estrogens and progestogens on bone and presents new data of the currently approved drospirenone-only pill. The use of progestin-only contraceptives leading to an estradiol level between 30 and 50 pg/ml does not seem to lead to an accelerate bone loss.

Cost-effectiveness of pharmacological fracture prevention for osteoporosis as prescribed in clinical practice in France, Germany, Italy, Spain, and the United Kingdom.

This study estimated the cost-effectiveness of pharmacological fracture prevention as prescribed in the five largest European countries (EU5) using the IOF reference cost-effectiveness model. Pharmacological fracture prevention as prescribed in clinical practice was cost-saving (provided more QALYs at lower costs) compared to no treatment in each of the EU5. PURPOSE: To estimate the real-world cost-effectiveness of pharmacological fracture prevention as prescribed in the five largest European countries by population size: France, Germany, Italy, Spain, and the United Kingdom (UK) (collectively EU5). MATERIALS AND METHODS: We analyzed sales data on osteoporosis drugs in each of the EU5 to derive a hypothetical intervention that corresponds to the mix of osteoporosis medication prescribed in clinical practice. The costs for this treatment mix were obtained directly from the sales data, and the efficacy of the treatment mix was estimated by weighing the treatment-specific fracture risk reductions from a published meta-analysis. Subsequently, we estimated the cost-effectiveness using costs per quality adjusted life year (QALY) of the intervention compared to no treatment in each of the EU5 using the International Osteoporosis Foundation (IOF) reference cost-effectiveness model. The model population comprised postmenopausal women, mean age 72 years with established osteoporosis (T-score ≤ - 2.5) among whom 23.6% had a prevalent vertebral fracture. The model was populated with country-specific data from the literature. RESULTS: Pharmacological fracture prevention as prescribed in clinical practice was cost-saving (provided more QALYs at lower costs) compared to no treatment in each country. The findings were robust in scenario analyses. CONCLUSIONS: Pharmacological fracture prevention as prescribed in clinical practice is cost-saving in each of the EU5. Because of the under-diagnosis and under-treatment of post-menopausal osteoporosis, from a health economic perspective, further cost-savings may be reached by expanding treatment to those at increased risk of fracture currently not receiving any treatment.

Bone health in childhood cancer: review of the literature and recommendations for the management of bone health in childhood cancer survivors.

In the past decades, new cancer treatment approaches for children and adolescents have led to a decrease in recurrence rates and an increase in long-term survival. Recent studies have focused on the evaluation of the late effects on bone of pediatric cancer-related treatments, such as chemotherapy, radiation and surgery. Treatment of childhood cancer can impair the attainment of peak bone mass, predisposing to premature onset of low bone mineral density, or causing other bone side-effects, such as bone quality impairment or avascular necrosis of bone. Lower bone mineral density and microarchitectural deterioration can persist during adulthood, thereby increasing fracture risk. Overall, long-term follow-up of childhood cancer survivors is essential to define specific groups at higher risk of long-term bone complications, identify unrecognized long-term adverse effects, and improve patient care. Children and adolescents with a cancer history should be carefully monitored, and patients should be informed of possible late complications of their previous medical treatment. The International Osteoporosis Foundation convened a working group to review the bone complications of pediatric cancer survivors, outlining recommendations for the management of bone health, in order to prevent and treat these complications.

Bone management in hematologic stem cell transplant recipients.

Autologous and allogeneic hematopoietic stem cell transplantation (HSCT) is the treatment of choice for patients with some malignant and non-malignant hematological diseases. Advances in transplantation techniques and supportive care measures have substantially increased the number of long-term HSCT survivors. This has led to an increasing patient population suffering from the late effects of HSCT, of which, bone loss and its consequent fragility fractures lead to substantial morbidity. Altered bone health, with consequent fragility fractures, and chronic graft-versus-host disease (GVHD) are factors affecting long-term quality of life after HSCT. Hypogonadism, HSCT preparative regimens, nutritional factors, and glucocorticoids all contribute to accelerated bone loss and increased fracture risk. Management strategies should include bone mineral density examination, evaluation of clinical risk factors, and general dietary and physical activity measures. Evidence has accumulated permitting recommendations for more attentiveness to evaluation and monitoring of bone health, with appropriate application of osteoporosis pharmacotherapies to patients at increased risk of bone loss and fracture.

The tamoxifen paradox-influence of adjuvant tamoxifen on fracture risk in pre- and postmenopausal women with breast cancer.

Our data demonstrate that tamoxifen does not reduce fracture risk. Close surveillance is necessary to prevent bone loss in premenopausal women with breast cancer upon treatment initiation. INTRODUCTION: Endocrine treatment of breast cancer may interfere with bone turnover and influence fracture risk. METHODS: Out of a cohort of almost 5 million patients in total, we identified 5520 women between 18 and 90 years of age with breast cancer receiving tamoxifen, matched them with 5520 healthy controls using the Disease Analyzer Database, and investigated the fracture risk. RESULTS: We found a cumulative incidence of fractures of 6.3% in patients aged between 18 and 50 years (n = 3634) treated with tamoxifen versus a cumulative incidence of 3.6% in the control group (p < 0.001). As such, the risk of fracture was 75% higher for patients receiving tamoxifen than that for healthy controls (HR 1.75; 95% CI 1.25-2.48). With regard to patients aged between 55 and 90 years (n = 7406), the cumulative incidence of fractures in patients treated with tamoxifen was 10.1% compared to 9.3% in the control group (p = 0.740), i.e., there was no significant difference between the two groups (HR 0.97; 95% CI 0.81-1.16). CONCLUSIONS: Compared to healthy controls, premenopausal women with breast cancer treated with tamoxifen showed an increased risk of fracture, while postmenopausal women on tamoxifen did not show any risk reduction.

Influence of side-effects on early therapy persistence with letrozole in post-menopausal patients with early breast cancer: Results of the prospective EvAluate-TM study.

BACKGROUND: Endocrine treatment (ET) with an aromatase inhibitor (AI) is the treatment of choice in post-menopausal patients with hormone receptor-positive early breast cancer (EBC). However, adverse events (AEs) often lead to treatment discontinuation. This analysis aimed to identify side-effects that lead to patients failing to persist with letrozole treatment. PATIENTS AND METHODS: Post-menopausal hormone receptor-positive EBC patients starting ET with letrozole were enroled in EvAluate-TM, a non-interventional study. Information regarding treatment compliance and persistence was gathered in months 6 and 12. Persistence was defined as the time from 30 d after the start to the end of treatment. The influence on persistence of musculoskeletal syndrome, menopausal disorder, sleep disorder and other AEs within the first 30 d was analysed using Cox regression analyses. RESULTS: Among 3887 patients analysed, the persistence rate after 12 months was >85%. In all, 568 patients (14.6%) discontinued the treatment, 358 of whom (63.0%) did so only because of side-effects. The main AEs influencing persistence were musculoskeletal symptoms (hazard ratio [HR] 2.55; 95% confidence interval [CI], 1.90-3.42), sleep disorders (HR 1.95; 95% CI, 1.41-2.70) and other AEs (HR 2.03; 95% CI, 1.51-2.73). Menopausal disorder was not associated with non-persistence (HR 1.17; 95% CI, 0.74-1.84). CONCLUSIONS: These results suggest that side-effects of AIs such as musculoskeletal syndrome and sleep disorder lead to ET discontinuation within the first treatment year in significant numbers of EBC patients. Compliance programmes adapted for subgroups that are at risk for early non-persistence might help to ensure the recommended therapy duration. CLINICAL TRIALS NUMBER: CFEM345DDE19.

Influence of patient and tumor characteristics on early therapy persistence with letrozole in postmenopausal women with early breast cancer: results of the prospective Evaluate-TM study with 3941 patients.

Background: Patients' compliance and persistence with endocrine treatment has a significant effect on the prognosis in early breast cancer (EBC). The purpose of this analysis was to identify possible reasons for non-persistence, defined as premature cessation of therapy, on the basis of patient and tumor characteristics in individuals receiving adjuvant treatment with letrozole. Patients and methods: The EvAluate-TM study is a prospective, multicenter, noninterventional study in which treatment with the aromatase inhibitor letrozole was evaluated in postmenopausal women with hormone receptor-positive EBC in the early therapy phase. Treatment persistence was evaluated at two pre-specified study visits after 6 and 12 months. As a measure of early therapy persistence the time from the start to the end of treatment (TTEOT) was analyzed. Cox regression analyses were carried out to identify patient characteristics and tumor characteristics predicting TTEOT. Results: Out of the total population of 3941 patients with EBC, 540 (13.7%) events involving treatment cessation unrelated to disease progression were observed. This was due to drug-related toxicity in the majority of cases (73.5%). Persistence rates were 92.2%, 86.9%, and 86.3% after 6, 12, and 15 months, respectively. The main factors influencing premature treatment discontinuation were older age [hazard ratio (HR) 1.02/year], comorbidities (HR 1.06 per comorbidity), low body mass index, and lower tumor grade (HR 0.85 per grade unit). Conclusion: These results support the view that older, multimorbid patients with low tumor grade and low body mass index are at the greatest risk for treatment discontinuation and might benefit from compliance and support programs.

Subsequent fracture risk of women with pregnancy and lactation-associated osteoporosis after a median of 6 years of follow-up.

Almost a quarter of patients with PAO will sustain a subsequent fracture; patients need to be informed about potential risks before deciding for further pregnancies. INTRODUCTION: Pregnancy and lactation-associated osteoporosis (PAO) is a severe type of premenopausal osteoporosis which predominantly occurs in the last trimester of pregnancy or immediately postpartum. Long-term follow-up data including subsequent fracture risk have yet to be reported. METHODS: This single-center prospective cohort study investigated the subsequent fracture risk of all 107 patients with PAO who were referred to our institution. RESULTS: Overall, 107 presented with at least one fracture. Each patient sustained on average four fractures most commonly at the thoracolumbar spine. During a median of 6 years of follow-up, 26 (24.3%) of patients who had a fracture at baseline reported a subsequent fracture. Overall, 30 PAO patients (28%) reported a further pregnancy. In subsequent pregnancies, 6 (20%) of patients reported a subsequent fracture. Patients with up to 1 vs. > 1 fracture at time of diagnosis showed a 3 (10%) and 25 (27%) subsequent fracture rate, respectively (p = 0.047). There was a significant correlation between the number of fractures at time of diagnosis and subsequent fracture risk (N = 26,p= 0.56, p = 0.003). CONCLUSIONS: Almost a quarter of patients with PAO will sustain a subsequent fracture, and this fracture risk correlates with the number of fractures at time of diagnosis. Patients with PAO need to be informed about their potential subsequent fracture risk before deciding for further pregnancies.

Factors associated with high 24-month persistence with denosumab: results of a real-world, non-interventional study of women with postmenopausal osteoporosis in Germany, Austria, Greece, and Belgium.

Persistence with osteoporosis therapy is vital for fracture prevention. This non-interventional study of postmenopausal women receiving denosumab in Germany, Austria, Greece, and Belgium found that persistence with denosumab remains consistently high after 24 months in patients at high risk of fracture. PURPOSE: Continued persistence with osteoporosis therapy is vital for fracture prevention. This non-interventional study of clinical practice evaluated medication-taking behavior of postmenopausal women receiving denosumab in Germany, Austria, Greece, and Belgium and factors influencing persistence. METHODS: Subcutaneous denosumab (60 mg every 6 months) was assigned according to prescribing information and local guidelines before and independently of enrollment; outcomes were recorded during routine practice for up to 24 months. Persistence was defined as receiving the subsequent injection within 6 months + 8 weeks of the previous injection and adherence as administration of subsequent injections within 6 months ± 4 weeks of the previous injection. Medication coverage ratio (MCR) was calculated as the proportion of time a patient was covered by denosumab. Associations between pre-specified baseline covariates and 24-month persistence were assessed using multivariable logistic regression. RESULTS: The 24-month analyses included 1479 women (mean age 66.3-72.5 years) from 140 sites; persistence with denosumab was 75.1-86.0%, adherence 62.9-70.1%, and mean MCR 87.4-92.4%. No covariate had a significant effect on persistence across all four countries. For three countries, a recent fall decreased persistence; patients were generally older with chronic medical conditions. In some countries, other covariates (e.g., older age, comorbidity, immobility, and prescribing reasons) decreased persistence. Adverse drug reactions were reported in 2.3-6.9% patients. CONCLUSIONS: Twenty-four-month persistence with denosumab is consistently high among postmenopausal women in Europe and may be influenced by patient characteristics. Further studies are needed to identify determinants of low persistence.

Oral contraceptive use and fracture risk-a retrospective study of 12,970 women in the UK.

In the present retrospective case-control study, we compared 6485 women with fractures and 6485 women without fractures from 135 general practitioner offices in the UK. Women without bone fractures were statistically more likely to have been exposed to oral contraception, depending on their age and therapy duration. INTRODUCTION: The aim of this analysis was to compare the risk of bone fracture in women using hormonal contraception with that in women who have never used hormonal contraception. METHODS: A total of 6485 women (mean age 37.8 years) with an initial diagnosis of fracture between January 2010 and December 2015 were identified in 135 doctors' offices in the UK Disease Analyzer database. In this nested case-control study, each case with a fracture was matched (1:1) to a control without a fracture for age, index year, and follow-up time. In total, 12,970 individuals were available for analysis. The main outcome of the study was the risk of fracture as a function of combined oral contraceptive (OC) therapy. Multivariate logistic regression models were used to determine the effect of OC therapy and its duration on the risk of fracture in the entire population and in four age-specific subgroups. RESULTS: Women without bone fractures were significantly more likely to have used oral contraception (OR 0.81). The usage of oral contraception was associated with a significantly lower risk of bone fracture (OR 0.81, 95% CI 0.74-0.90). This effect was strongest in the age groups 18-25 and 26-35 and in patients with an OC treatment duration of more than 1 year. CONCLUSIONS: The present study revealed that women without bone fractures were significantly more likely to have had exposure to combined oral contraception, especially where the duration of intake was at least 5 years.