Teriparatide and bone turnover and formation in a hemodialysis patient with low-turnover bone disease: a case report.

Teriparatide, a recombinant form of parathyroid hormone, is an anabolic agent approved for use in women and men with osteoporosis. However, it is not well studied in people with chronic kidney disease (CKD). We report on a patient with stage 5 CKD treated with dialysis who presented to our clinic with multiple fractures, including bilateral nondisplaced pelvic fractures resulting in chronic pain and interfering with the patient's ability to work. Bone histomorphometry demonstrated low-turnover bone disease, and he was treated with 20µg of teriparatide (subcutaneous injection) every morning for 24 months. Within 6 months of initiating therapy, the patient's pain resolved and he was able to resume work. Serum calcium and phosphate levels remained within reference ranges throughout his treatment, and he sustained no further fractures. During 24 months of treatment, bone mineral density was maintained at the lumbar spine, and there was an increase of 4% at the femoral neck and total hip. A second transiliac bone biopsy demonstrated improvements in static and dynamic parameters of bone formation. In our patient, 24-month treatment with teriparatide was safe and effective; however, larger studies are needed to determine the efficacy of teriparatide in the dialysis-dependent CKD population.

Pasireotide monotherapy in Cushing's disease: a single-centre experience with 5-year extension of phase III Trial.

PURPOSE: A recent phase III randomized controlled trial (NCT00434148) showed efficacy of pasireotide in the treatment of patients with Cushing's disease (CD). Patients were invited to participate in an extension phase of the protocol and a subgroup had a sustained response. We report the experience with 4 patients in our center of which 2 full responders have completed 5.5 and 4.25 years of treatment with disease control. METHODS: The trial protocol was described previously. The extension phase consisted of 3-monthly visits with clinical, biochemical, and imaging evaluation and investigator-driven pasireotide titration. Research charts were retrospectively analyzed. RESULTS: Four patients with persistent CD following pituitary surgery completed the first 6 months of the trial and 3 continued in the next 6 month open-label phase. Two patients with baseline urinary free cortisol (UFC) 5.3-6.7 times the upper limit of normal had a rapid sustained response to pasireotide and entered the extension phase after 12 months. They remain in clinical and biochemical disease remission and 1 patient now only requires 300 µg daily of pasireotide. All 4 patients developed glucose intolerance; however, the two patients in the extension phase were eventually able to discontinue all diabetes pharmacotherapy. Adverse events included second degree atrioventicular block type 1 without QT prolongation in a patient with pre-existing sinus bradycardia, and symptomatic cholelithiasis requiring cholecystectomy in a second patient. CONCLUSIONS: Pasireotide therapy can provide normalization of UFC and of clinical symptoms and signs of CD during up to 5 years of follow-up. This study demonstrates the possible recuperation of normoglycemia after continued use of pasireotide and control of underlying hypercortisolemia. Longer-term monitoring for potential adverse events related to continued use of pasireotide is indicated.

Bisphosphonates for treatment of osteoporosis: expected benefits, potential harms, and drug holidays.

OBJECTIVE: To outline the efficacy and risks of bisphosphonate therapy for the management of osteoporosis and describe which patients might be eligible for bisphosphonate "drug holiday." QUALITY OF EVIDENCE: MEDLINE (PubMed, through December 31, 2012) was used to identify relevant publications for inclusion. Most of the evidence cited is level II evidence (non-randomized, cohort, and other comparisons trials). MAIN MESSAGE: The antifracture efficacy of approved first-line bisphosphonates has been proven in randomized controlled clinical trials. However, with more extensive and prolonged clinical use of bisphosphonates, associations have been reported between their administration and the occurrence of rare, but serious, adverse events. Osteonecrosis of the jaw and atypical subtrochanteric and diaphyseal femur fractures might be related to the use of bisphosphonates in osteoporosis, but they are exceedingly rare and they often occur with other comorbidities or concomitant medication use. Drug holidays should only be considered in low-risk patients and in select patients at moderate risk of fracture after 3 to 5 years of therapy. CONCLUSION: When bisphosphonates are prescribed to patients at high risk of fracture, their antifracture benefits considerably outweigh their potential for harm. For patients taking bisphosphonates for 3 to 5 years, reassess the need for ongoing therapy.

High-resolution peripheral quantitative computed tomography for the assessment of bone strength and structure: a review by the Canadian Bone Strength Working Group.

Bone structure is an integral determinant of bone strength. The availability of high resolution peripheral quantitative computed tomography (HR-pQCT) has made it possible to measure three-dimensional bone microarchitecture and volumetric bone mineral density in vivo, with accuracy previously unachievable and with relatively low-dose radiation. Recent studies using this novel imaging tool have increased our understanding of age-related changes and sex differences in bone microarchitecture, as well as the effect of different pharmacological therapies. One advantage of this novel tool is the use of finite element analysis modelling to non-invasively estimate bone strength and predict fractures using reconstructed three-dimensional images. In this paper, we describe the strengths and limitations of HR-pQCT and review the clinical studies using this tool.

Increased Imminent Fracture Risk in Liver Transplant Recipients Despite Bisphosphonate Therapy.

BACKGROUND: Bone loss is significant after orthotopic liver transplant (OLT) and is associated with increased fracture risk and decreased quality of life. In post-transplant fracture prevention, the cornerstone of therapeutic management is bisphosphonates. METHODS: We conducted a retrospective study in a cohort of 155 OLT recipients who received a bisphosphonate prescription at hospital discharge between 2012 and 2016 to investigate post-OLT fragility fracture incidence and predictive risk factors. RESULTS: Before OLT, 14 patients presented a T score < -2.5 SD, and 23 patients (14.8%) had a history of fracture. During follow-up, the cumulative incidence of fractures on bisphosphonates (99.4% risedronate/alendronate) was 9.7% at 12 months and 13.1% at 24 months. The median time to first fragility fracture was 10 months (IQR, 3-22 months) and thus within the first 2 years of follow-up. Predictive factors of fragility fractures in multivariate Cox regression analyses included age 60 years or older (hazard ratio [HR], 2.61; 95% CI, 1.14-6.01; P = .02), post-transplant diabetes mellitus (HR, 3.82; 95% CI, 1.55-9.44; P = .004), and cholestatic disease (HR, 5.93; 95% CI, 2.30-15.26; P = .0002). Additionally, the female sex was associated with a strong trend toward increased fracture risk in univariate analysis (HR, 2.27; 95% CI, 1.00-5.15; P = .05), as well as a post-transplant absolute decrease in bone mineral density at the femoral neck and total hip (P = .08). CONCLUSIONS: This real-world study reports a high incidence of fractures post-OLT despite bisphosphonate therapy. Age 60 years or older, post-transplant diabetes mellitus, cholestatic disease, female sex, and femoral neck and/or total hip bone mineral density loss contribute to increased imminent fracture risk in liver transplant recipients.

Prevention of COVID-19 with oral vitamin D supplemental therapy in essential healthcare teams (PROTECT): protocol for a multicentre, triple-blind, randomised, placebo-controlled trial.

INTRODUCTION: In the COVID-19 pandemic, healthcare workers (HCWs) were at high risk of infection due to their exposure to COVID infections. HCWs were the backbone of our healthcare response to this pandemic; every HCW withdrawn or lost due to infection had a substantial impact on our capacity to deliver care. Primary prevention was a key approach to reduce infection. Vitamin D insufficiency is highly prevalent in Canadians and worldwide. Vitamin D supplementation has been shown to significantly decrease the risk of respiratory infections. Whether this risk reduction would apply to COVID-19 infections remained to be determined. This study aimed to determine the impact of high-dose vitamin D supplementation on incidence of laboratory-confirmed COVID-19 infection rate and severity in HCWs working in high COVID incidence areas. METHODS AND ANALYSIS: PROTECT was a triple-blind, placebo-controlled, parallel-group multicentre trial of vitamin D supplementation in HCWs. Participants were randomly allocated in a 1:1 ratio in variable block size to intervention (one oral loading dose of 100 000 IU vitamin D3+10 000 IU weekly vitamin D3) or control (identical placebo loading dose+weekly placebo). The primary outcome was the incidence of laboratory-confirmed COVID-19 infection, documented by RT-qPCR on salivary (or nasopharyngeal) specimens obtained for screening or diagnostic purposes, as well as self-obtained salivary specimens and COVID-19 seroconversion at endpoint. Secondary outcomes included disease severity; duration of COVID-19-related symptoms; COVID-19 seroconversion documented at endpoint; duration of work absenteeism; duration of unemployment support; and adverse health events. The trial was terminated prematurely, due to recruitment difficulty. ETHICS AND DISSEMINATION: This study involves human participants and was approved by the Research Ethics Board (REB) of the Centre hospitalier universitaire (CHU) Sainte-Justine serving as central committee for participating institutions (#MP-21-2021-3044). Participants provided written informed consent to participate in the study before taking part. Results are being disseminated to the medical community via national/international conferences and publications in peer-reviewed journals. TRIAL REGISTRATION NUMBER: https://clinicaltrials.gov/ct2/show/NCT04483635.

Varying conceptions of competence: an analysis of how health sciences educators define competence.

CONTEXT: Current debate in medical education focuses on the nature of 'competency-based medical education' (CBME) and whether or not it should be adopted. Many medical schools claim to run 'competency-based' curricula, but the structure of their programmes can differ radically. A review of the existing CBME literature reveals that little attention has been paid to defining the concept of competence. A straightforward examination of what is meant by the term 'competence' is noticeably missing from the literature, despite its impact on medical training. OBJECTIVES: This paper aims to illustrate the varying conceptions of 'competence' by comparing and contrasting definitions provided in the health sciences education literature and discussing their respective impacts on medical education. METHODS: A systematic review of recent publications in medical education journals published in English and French was conducted to extract definitions of competence or, if definitions were not explicitly stated, to derive the authors' implicit conception of competence. A sample of 14 definitions from articles in the health sciences education field was studied using thematic analysis. RESULTS: There is agreement that competence is composed of knowledge, skills and other components. Although agreement about the nature of these other components is lacking, attitudes and values are suggested to be essential ingredients of competence. Furthermore, a clear divergence in conceptions of how a competent person utilises these components is apparent. One view specifies that competence involves selecting components according to specific situations, as required. A second view places greater emphasis on the synergy that results from the use of a combination of components in a given situation. CONCLUSIONS: These conceptual distinctions have many implications for the way CBME is implemented. A conception of competence as the selection of components may lead to a greater emphasis, in a training setting, on the mastery of each component separately. A conception of competence as the use of a combination of components leads to greater emphasis on the synergy that results as they are deployed in clinical situations.

Lenvatinib Therapy for Advanced Thyroid Cancer: Real-Life Data on Safety, Efficacy, and Some Rare Side Effects.

Context: The SELECT trial led to the approval of lenvatinib for the treatment of advanced radioiodine-refractory differentiated thyroid carcinomas (DTCs) but also revealed an important adverse event (AE) profile which may limit its use in clinical practice. Objective: We aim to describe the efficacy and toxicity profiles of lenvatinib in real life. Methods: We included all patients who received lenvatinib for an advanced DTC at our institution, enrolling 27 patients. We reviewed retrospectively electronic medical records to assess efficacy and AEs. Results: Among the 24 patients with evaluation of tumor response during treatment, overall response rate (ORR) was 37.0% (95% CI, 19.4%-57.6%), and disease control rate was 85.2% (95% CI, 66.3%-95.8%). The median progression-free survival (PFS) was 12 months (95% CI, 7.5-16.5]. The most prevalent AEs were hypertension (77.8%), fatigue (55.6%), and weight loss (51.9%). At least one grade ≥ 3 AE was experienced by 25/27 patients (92.6%), mostly hypertension (59.3%). Lenvatinib was discontinued due to AEs in 13/27 patients (48.1%). Interestingly, 1 patient experienced a grade 4 posterior reversible encephalopathy syndrome, and another developed a Takotsubo cardiomyopathy. Conclusion: The safety profile of lenvatinib in our cohort was similar to that reported in the literature, with a predominance of hypertension. Rigorous blood pressure control is therefore essential to avoid discontinuing therapy. We also report 2 severe and rarely described AEs that physicians should watch for. As for efficacy, although less than in the SELECT trial, ORR and PFS were similar to other real-life studies.

Oral vitamin D supplemental therapy to attain a desired serum 25-hydroxyvitamin D concentration in essential healthcare teams.

BACKGROUND: The study objectives were to ascertain the efficacy of vitamin D supplementation in rapidly increasing serum vitamin D and of implementation of a hybrid (virtual and in-person) trial. METHODS: In a randomized triple-blind controlled trial, healthcare workers were allocated to receive an oral bolus of 100,000 IU with 10,000 IU/week of vitamin D3 or placebo. The co-primary outcomes were the change from baseline in serum 25-hydroxyvitamin D [(Δ) 25(OH)D] and proportion with vitamin D sufficiency (25(OH)D ≥ 75 nmol/L), at endpoint. Adherence to supplements and procedures as well as adverse event rates were documented. RESULTS: Thirty-four (19 intervention, 15 control) subjects were randomized, with 28 (41%) virtual visits. After 44.78 ± 11.00 days from baseline, a significant adjusted group difference of 44.2 (34.7, 53.8) nmol/L was observed in the Δ 25(OH)D (95% CI) in favor of supplementation; 77.8% of intervention, and 13.3% of control, patients were vitamin D sufficient (OR:6.11, 95% CI:1.6, 22.9). The adherence to intervention was 94.7% in the intervention and 100% in the control groups. Irrespective of visit type, high adherence was observed in sampling procedures and completion of fortnightly online questionnaire. No adverse events attributable to vitamin D were reported. CONCLUSION: The vitamin D supplementation rapidly and safely raised 25(OH)D levels to sufficient levels for a biological effect. Similarly high adherence to study procedures was observed with virtual and in-person participation. TRIAL REGISTRATION: This trial was registered at https://clinicaltrials.gov on July 23, 2020 (# NCT04483635 ).

Mutations in NOTCH2 in families with Hajdu-Cheney syndrome.

Hajdu-Cheney syndrome (HCS) is a rare genetic disorder whose hallmark is acro-osteolysis, shortening of terminal phalanges, and generalized osteoporosis. We assembled a cohort of seven families with the condition and performed whole exome resequencing on a selected set of affected patients. One protein-coding gene, NOTCH2, carried heterozygous truncating variants in all patients and their affected family members. Our results replicate recently published studies of HCS and further support this as the causal gene for the disorder. In total, we identified five novel and one previously reported mutation, all clustered near the carboxyl terminus of the gene, suggesting an allele specific genotype-phenotype effect since other mutations in NOTCH2 have been reported to cause a form of Alagille syndrome. Notch-mediated signaling is known to play a role in bone metabolism. Our results support a potential therapeutic role for Notch pathways in treatment of osteoporosis.

Prediction of Osteoporotic Fractures in Elderly Individuals: A Derivation and Internal Validation Study Using Healthcare Administrative Data.

In Canada and other countries, osteoporosis is monitored as part of chronic disease population surveillance programs. Although fractures are the principal manifestation of osteoporosis, very few algorithms are available to identify individuals at high risk of osteoporotic fractures in current surveillance systems. The objective of this study was to derive and validate predictive models to accurately identify individuals at high risk of osteoporotic fracture using information available in healthcare administrative data. More than 270,000 men and women aged ≥66 years were randomly selected from the Quebec Integrated Chronic Disease Surveillance System. Selected individuals were followed between fiscal years 2006-2007 and 2015-2016. Models were constructed for prediction of hip/femur and major osteoporotic fractures for follow-up periods of 5 and 10 years. A total of 62 potential predictors measurable in healthcare administrative databases were identified. Predictor selection was performed using a manual backward algorithm. The predictive performance of the final models was assessed using measures of discrimination, calibration, and overall performance. Between 20 and 25 predictors were retained in the final prediction models (eg, age, sex, social deprivation index, most of the major and minor risk factors for osteoporosis, diabetes, Parkinson's disease, cognitive impairment, anemia, anxio-depressive disorders). Discrimination of the final models was higher for the prediction of hip/femur fracture than major osteoporotic fracture and higher for prediction for a 5-year than a 10-year period (hip/femur fracture for 5 years: c-index = 0.77; major osteoporotic fracture for 5 years: c-index = 0.71; hip/femur fracture for 10 years: c-index = 0.73; major osteoporotic fracture for 10 years: c-index = 0.68). The predicted probabilities globally agreed with the observed probabilities. In conclusion, the derived models had adequate predictive performance in internal validation. As a final step, these models should be validated in an external cohort and used to develop indicators for surveillance of osteoporosis. © 2021 American Society for Bone and Mineral Research (ASBMR).

Duration-Dependent Increase of Human Bone Matrix Mineralization in Long-Term Bisphosphonate Users with Atypical Femur Fracture.

Bisphosphonates (BPs) are the most widely used drugs for the treatment of osteoporosis but prolonged use of BPs might increase the risk of atypical femur fracture (AFF). There are only a few studies that address the bone material quality in patients on long-term BP treatment with or without AFFs. We analyzed 52 trans-iliac bone biopsies from patients on long-term BP therapy with (n = 26) and without (n = 26) AFF. At the microscopic level, the degree of mineralization of bone (DMB) was assessed on whole bone by X-ray digitized microradiography while microhardness by Vickers microindentation, and bone matrix characteristics by Fourier transform infrared microspectroscopy (FTIRM) (mineral/organic ratio, mineral maturity and crystallinity, and collagen maturity) were measured at random focal areas. The AFF patients were treated longer than non-AFF patients (9.7 ± 3.3 years versus 7.9 ± 2.7 years). As expected, bone remodeling was low in both groups, without difference between them. The AFF group had significantly higher DMB in cortical bone (+2.9%, p = .001), which remained so after adjusting for treatment duration (p = .007), and showed a trend in cancellous bone (+1.6%, p = .05). Consistent with higher DMB, heterogeneity index (HI) was lower in the AFF than in the non-AFF group, illustrating lower heterogeneity of mineralization in the AFF group. A significant positive correlation between the duration of treatment and DMB in cortical bone was found in AFF, and not in the non-AFF group. Microhardness and bone matrix characteristics were similar between groups. We conclude that the AFF group had a duration-dependent increase in DMB leading to a significantly higher DMB than the non-AFF. Because BPs have high affinity to bone mineral and lining the walls of the osteocyte lacunae, the accumulation of matrix-bound BPs in AFF could lead to inhibition of the osteocyte cytoskeleton blunting their response to mechanical strains, a hypothesis to be further investigated. © 2021 American Society for Bone and Mineral Research (ASBMR).

Autocrine regulation of interferon gamma in mesenchymal stem cells plays a role in early osteoblastogenesis.

Interferon (IFN)gamma is a strong inhibitor of osteoclast differentiation and activity. However, its role in osteoblastogenesis has not been carefully examined. Using microarray expression analysis, we found that several IFNgamma-inducible genes were upregulated during early phases of osteoblast differentiation of human mesenchymal stem cells (hMSCs). We therefore hypothesized that IFNgamma may play a role in this process. We first observed a strong and transient increase in IFNgamma production following hMSC induction to differentiate into osteoblasts. We next blocked this endogenous production using a knockdown approach with small interfering RNA and observed a strong inhibition of hMSC differentiation into osteoblasts with a concomitant decrease in Runx2, a factor indispensable for osteoblast development. Additionally, exogenous addition of IFNgamma accelerated hMSC differentiation into osteoblasts in a dose-dependent manner and induced higher levels of Runx2 expression during the early phase of differentiation. We next examined IFNgamma signaling in vivo in IFNgamma receptor 1 knockout (IFNgammaR1(-/-)) mice. Compared with their wild-type littermates, IFNgammaR1(-/-) mice exhibited a reduction in bone mineral density. As in the in vitro experiments, MSCs obtained from IFNgammaR1(-/-) mice showed a lower capacity to differentiate into osteoblasts. In summary, we demonstrate that the presence of IFNgamma plays an important role during the commitment of MSCs into the osteoblastic lineage both in vitro and in vivo, and that this process can be accelerated by exogenous addition of IFNgamma. These data therefore support a new role for IFNgamma as an autocrine regulator of hMSC differentiation and as a potential new target of bone-forming cells in vivo.

Comparison of the effects of once-monthly versus once-daily risedronate in postmenopausal osteoporosis: a phase II, 6-month, multicenter, randomized, double-blind, active-controlled, dose-ranging study.

BACKGROUND: Risedronate 5 mg/d is approved by the US Food and Drug Administration for the treatment and prevention of postmenopausal osteoporosis. Once-monthly dosing options might increase treatment compliance and persistence. OBJECTIVE: The aim of this study was to compare the tolerability and efficacy of 3 once-monthly risedronate dosing regimens with those of risedronate 5 mg/d. METHODS: This Phase II, 6-month, randomized, double-blind, active-controlled, dose-ranging study was conducted at 13 clinical research centers and hospitals in Croatia, Poland, Canada, and the United States between April 2004 and June 2005. Post-menopausal women aged 50 to 85 years with a lumbar spine T-score <-2.0 were randomly assigned to 1 of 4 treatment groups: risedronate 100, 150, or 200 mg/mo or 5 mg/d (active control), administered PO for 6 months. Evaluation of tolerability, the primary study objective, was based on adverse-event (AE) profiles and clinical laboratory values. Efficacy evaluation, a secondary objective, was a noninferiority comparison of the changes from baseline in bone mineral density (BMD) and bone turnover markers (BTMs). RESULTS: Of 370 patients randomized (91, 88, 88, and 103 patients in the risedronate 100-, 150-, and 200-mg/mo and 5-mg/d groups, respectively), 57% were > or =65 years of age and 99% were white; 316 patients (85.4%) completed the study. Completion rates were not significantly different across treatment groups, nor were reasons for discontinuation. Between-group differences in the incidences of treatment-emergent AEs, serious AEs, and upper gastrointestinal (GI) AEs were nonsignificant. Overall, 6 (7%), 14 (16%), 6 (7%), and 9 patients (9%) withdrew because of AEs in the 100-, 150-, and 200-mg/mo and 5 mg/d groups, respectively. GI disorders were the AEs that most frequently led to study withdrawal (5 [5.5%], 7 [8.0%], 4 [4.5%], and 6 [5.8%]). No trends were observed in the nature or frequency of other AEs causing withdrawal. All serious AEs were considered unrelated to treatment, with the exception of erosive esophagitis in 1 patient (1%) who received the 5-mg/d dose. Mean percentage increases in BMD were 2.10%, 2.99%, and 3.38% with risedronate 100, 150, and 200 mg/mo, respectively, versus 3.05% with 5 mg/d. At the 2 higher monthly doses, the changes from baseline in BMD were not significantly different from those in the 5-mg/d group. Mean BTM values were decreased significantly from baseline in all 4 treatment groups, and the changes from baseline at 6 months at the 2 higher monthly doses were not significantly different from those at 5 mg/d. CONCLUSIONS: Overall, in this study, the safety profiles of risedronate 100, 150, and 200 mg/mo were not different from that of risedronate 5 mg/d. Changes in efficacy measures in the monthly treatment groups were considered dose related and were not significantly different between the 5-mg/d group and the 150- and 200-mg/mo groups; similarity was greatest with 150 mg/mo.

Oral ibandronate preserves trabecular microarchitecture: micro-computed tomography findings from the oral iBandronate Osteoporosis vertebral fracture trial in North America and Europe study.

Micro-computed tomography (micro-CT) is a quantitative 3-dimensional (3D) scanning procedure used to assess trabecular architecture. In the 3-yr oral iBandronate Osteoporosis vertebral fracture trial in North America and Europe (BONE) study, it was found that oral ibandronate administered daily (2.5 mg) or intermittently (20 mg) significantly reduced vertebral fracture risk by 62% (p=0.0001) and 50% (p=0.0006), respectively, vs placebo. Two-dimensional histomorphometric analysis of BONE study biopsies indicated that newly formed bone was of normal quality. In the current analysis, micro-CT was used to assess 3D trabecular microarchitecture. Rod and plate distribution was quantified by differential analysis of the triangulated bone surface. Biopsies were obtained from 110 patients, with 84 evaluable by micro-CT. Median structural model index (SMI; a lower SMI indicates an increased ratio of plates to rods and thus, improved trabecular microarchitecture) was 1.001 with ibandronate vs 1.365 with placebo (90% confidence interval [CI] for difference in medians: -0.626, -0.033), and connectivity density was higher in ibandronate-treated patients (median: 3.904 vs 3.112/mm3, 90% CI for difference in medians: 0.159, 1.517). This indicates that trabecular microarchitecture was better preserved in patients receiving ibandronate than placebo. Taken together with previous results from BONE, these findings indicate that ibandronate treatment preserves bone strength by maintaining good quality trabecular microarchitecture in women with postmenopausal osteoporosis.

Impact of noncompliance with alendronate and risedronate on the incidence of nonvertebral osteoporotic fractures in elderly women.

AIMS: To evaluate the association between noncompliance with alendronate and risedronate and the risk of nonvertebral osteoporotic fracture in community-dwelling elderly women. METHODS: A nested case-control study was conducted using the Quebec administrative health databases. To be included in the cohort, women needed to be aged > or = 68 years and to have initiated treatment with alendronate or risedronate between 1 January 2002 and 31 March 2005. Cases consisted of all women with an incident nonvertebral osteoporotic fracture occurring > or = 1 year after initiation of therapy. Each case was matched with up to 20 controls using incidence density sampling, according to age (+/- 1 year) and follow-up duration. A woman was noncompliant if she had a medication possession ratio (MPR) <80% for total follow-up duration. Rate ratios (RR) for fracture were estimated through conditional logistic regression analysis, adjusting for potential confounders. RESULTS: Among the 30 259 women included in the cohort, 1036 nonvertebral fracture cases were identified and were matched to 20 069 controls. Compared with women with a MPR > or = 80%, those with a MPR < 80% had a greater risk of nonvertebral fracture [adjusted RR 1.27, 95% confidence interval (CI) 1.12, 1.44]. Considering hip fracture only, the multivariate model yielded similar results, (adjusted RR 1.28, 95% CI 1.02, 1.61). CONCLUSIONS: Among community-dwelling elderly women, noncompliance with alendronate or risedronate is associated with an increased risk of nonvertebral fracture.

Recognizing osteoporosis and its consequences in Quebec (ROCQ): background, rationale, and methods of an anti-fracture patient health-management programme.

Recognizing Osteoporosis and its Consequences in Quebec (ROCQ) is an ongoing patient health-management programme aimed at evaluating the diagnostic and treatment care gaps for osteoporosis following a fragility fracture, and subsequently initiating and measuring interventions to decrease these gaps in women 50 years of age and over. Hospitals servicing approximately half of the population of the Province of Quebec (Canada) are participating in the ROCQ programme. Women with fragility and traumatic fractures are approached during their visit to a cast or outpatient clinic and are subsequently contacted by telephone 0 to 16 weeks after their fracture (phase 1). During the first phone contact, they are invited to answer a questionnaire aimed at identifying the specific circumstances of their fracture and asked to participate in an observational study that could last up to 18 months. Based on this initial questionnaire, patients are classified as having either experienced a fragility or traumatic fracture. During the first phone contact, there is no reference about the possible association between the fracture and osteoporosis and no investigation or intervention is proposed. Six to eight months after the fracture event (phase 2), women are again contacted by phone to complete a questionnaire that evaluates the diagnostic and treatment rates for osteoporosis. At this phase of the programme, women with fragility fractures are randomized to one of the three following intervention groups: 1) Educational Video Group, 2) Documentation Group and 3) Control Group. Participants are contacted 12 to 14 months after the intervention (phase 3) to evaluate the efficacy of the interventions on the diagnosis and treatment rates of osteoporosis. All participants with fragility or traumatic fractures who consent will be followed for 20 years using data from the Québec Ministry of Health database to measure the association between the index fracture and future fracture risk.

Population-based study of the effectiveness of bone-specific drugs in reducing the risk of osteoporotic fracture.

AIM: Evidence supports bone-specific drugs (BSDs) efficacy in the fracture risk reduction. But treatment rates for osteoporosis among high-risk patients are far below the recommended guidelines. A major concern about BSDs is the lack of adherence with treatment. OBJECTIVE: To determine if BSDs decrease fracture risk in high-risk elderly women in real clinical setting. METHODS: A nested case-control design was used in a cohort of elderly women from the Quebec health databases. Women enter into the cohort if they are 70 years or older between 1995 and 2003. Nested case-controls were designed for women with a diagnosis of osteoporosis (OP) and for those with a prior fracture. All cases of fractures occurring during follow-up were matched with 10 randomly selected controls based on age, time period, bone mass density testing, and having a diagnosis of OP or a prior fracture. Use of BSDs before the index date was categorized as follows: short-term (< or =1 year), intermediate-term (>1 and < or = 3 years), and long-term (>3 years). We used an adjusted conditional logistic regression model to assess BSD effect on fracture. RESULTS: Among 3170 women who had a fracture, of these women, 1824 had OP and 1346 had a prior fracture. Only long-term exposure to BSDs among women with OP reduced the fracture risk by 16% (odds ratio: 0.84; 0.73-0.97). Among women with OP, a high number of medical services or use of anticonvulsants or narcotics increased the fracture risk by 12-73%. Among women with a prior fracture, a high number of medical services or risk of fall or use of benzodiazepines, antidepressants, or narcotics increased the fracture risk by 23-77%. CONCLUSION: The incidence of fractures decreased by 16% among women with OP when more than 80% of BSDs was used for at least 3 years. Among women with a prior fracture, fracture risk reduction was not significant. Exposure to BSDs among women with a prior fracture is troubling, given that only approximately 12% of these individuals were being treated, and only 2% was using BSDs for the long term.

Hypomagnesemia During Teriparatide Treatment in Osteoporosis: Incidence and Determinants.

In our clinical experience, we have encountered patients who developed hypomagnesemia after the introduction of teriparatide. Some trials have reported hypomagnesemia as an adverse event during teriparatide treatment, but this issue had never been studied specifically. Our objective was twofold: 1) determine the incidence of hypomagnesemia (serum magnesium <0.7 mmol/L) associated with teriparatide in a retrospective cohort and 2) identify the predisposing factors to hypomagnesemia in this cohort. We reviewed the files of 53 patients treated for severe osteoporosis with teriparatide for 6 to 24 months between May 2008 and January 2016. Serum magnesium levels were measured at 0, 3, 6, 12, 18, and 24 months. In the full cohort, we observed an average decrease of serum magnesium of 0.075 mmol/L, 0.069 mmol/L, 0.085 mmol/L, 0.086 mmol/L (p < 0.001) at 3, 6, 12 months, and at the end of the treatment, respectively. The cumulative incidence of hypomagnesemia during treatment with teriparatide was 35.9% (19 patients). Patients' older age (71.1 versus 65.1 years; p = 0.05) and lower baseline level of magnesium before teriparatide treatment (0.81 mmol/L versus 0.85 mmol/L; p = 0.03) were significant risk factors for teriparatide-induced hypomagnesemia. The average decrease of serum magnesium was greater in the patients who developed hypomagnesemia compared with normomagnesemic patients at 3 months (0.110 mmol/L versus 0.054 mmol/L; p = 0.02), 6 months (0.139 mmol/L versus 0.036 mmol/L; p < 0.001), and 12 months (0.156 mmol/L versus 0.048 mmol/L; p < 0.001). Serum calcium, creatinine, and parathyroid hormone remained normal throughout the treatment period. We observed a statistically significant decrease in the serum magnesium levels in patients treated with teriparatide for severe osteoporosis. Older age and lower baseline magnesium were significant determinants of hypomagnesemia. Closer monitoring of serum magnesium level should be considered in these patients. © 2018 American Society for Bone and Mineral Research.