Pathogenesis, assessment, and management of bone loss in axial spondyloarthritis.

INTRODUCTION: Axial spondyloarthritis (axSpA) presents a complex scenario where both new bone formation in entheseal tissues and significant trabecular bone loss coexist, emphasizing the intricate nature of bone dynamics in this context. METHODS: A search of the literature was conducted to compose a narrative review exploring the pathogenesis, possible assessment methods, and potential management options for axSpA. RESULTS: While chronic systemic and local inflammation contribute to bone loss, the mechanisms behind axSpA-associated bone loss exhibit distinct characteristics influenced by factors like mechanical stress and the gut microbiome. These factors directly or indirectly stimulate osteoclast differentiation and activation through the RANK-RANKL axis, while simultaneously impeding osteoblast differentiation via negative regulation of bone anabolic pathways, including the Wnt signaling pathway. This disruption in the balance between bone-resorbing osteoclasts and bone-forming osteoblasts contributes to overall bone loss in axSpA. Early evaluation at diagnosis is prudent for detecting bone changes. While traditional dual x-ray absorptiometry (DXA) has limitations due to potential overestimation from spinal new bone formation, alternative methods like trabecular bone score (TBS), quantitative CT (QCT), and quantitative ultrasound (QUS) show promise. However, their integration into routine clinical practice remains limited. In addition to approved anti-inflammatory drugs, lifestyle adjustments like regular exercise play a key role in preserving bone health. Tailoring interventions based on individual risk profiles holds potential for mitigating bone loss progression. CONCLUSION: Recognizing the pivotal role of bone loss in axSpA underscores the importance of integrating regular assessments and effective management strategies into clinical practice. Given the multifaceted contributors to bone loss in axSpA, a multidisciplinary approach is essential.

Combination analgesic development for enhanced clinical efficacy (the CADENCE trial): a double-blind, controlled trial of an alpha-lipoic acid-pregabalin combination for fibromyalgia pain.

ABSTRACT: Drug therapy for fibromyalgia is limited by incomplete efficacy and dose-limiting adverse effects (AEs). Combining agents with complementary analgesic mechanisms-and differing AE profiles-could provide added benefits. We assessed an alpha-lipoic acid (ALA)-pregabalin combination with a randomized, double-blind, 3-period crossover design. Participants received maximally tolerated doses of ALA, pregabalin, and ALA-pregabalin combination for 6 weeks. The primary outcome was daily pain (0-10); secondary outcomes included Fibromyalgia Impact Questionnaire, SF-36 survey, Medical Outcomes Study Sleep Scale, Beck Depression Inventory (BDI-II), adverse events, and other measures. The primary outcome of daily pain (0-10) during ALA (4.9), pregabalin (4.6), and combination (4.5) was not significantly different ( P = 0.54). There were no significant differences between combination and each monotherapy for any secondary outcomes, although combination and pregabalin were both superior to ALA for measures of mood and sleep. Alpha-lipoic acid and pregabalin maximal tolerated doses were similar during combination and monotherapy, and AEs were not frequent with combination therapy. These results do not support any additive benefit of combining ALA with pregabalin for fibromyalgia. The observation of similarly reached maximal tolerated drug doses of these 2 agents (which have differing side-effect profiles) during combination and monotherapy-without increased side effects-provides support for future development of potentially more beneficial combinations with complementary mechanisms and nonoverlapping side effects.

Systematic Review of Non-surgical Therapies for Osteoarthritis of the Hand: An Update.

Hand osteoarthritis is a common disease with significant morbidity. This review aimed to update our earlier systematic reviews which included all published randomized controlled trials evaluating pharmacological and non-pharmacological therapies in patients with hand osteoarthritis. A total of 133 randomized controlled trials evaluating pharmacological and nonpharmacological therapies in hand osteoarthritis were reviewed. Overall, the methodological quality of randomized controlled trials has improved since the last update. Almost all new studies described their methods for randomization, blinding, and allocation concealment. However, studies continued to underreport features specific to hand osteoarthritis, such as pattern of joint involvement and number of affected joints. Standardized outcome assessments for pain and function were commonly presented, but measures of other hand osteoarthritis specific outcomes, such as health-related quality of life and patient global assessments, continued to be underreported. Future trials should consistently report on hand osteo arthritis specific features and outcome assessments in order to make clinically relevant conclusions about the efficacy of the diverse treatment options available.

CanVasc consensus recommendations for the use of avacopan in antineutrophil cytoplasm antibody-associated vasculitis: 2022 addendum.

OBJECTIVE: In 2020, the Canadian Vasculitis Research Network (CanVasc) published their updated recommendations for the management of ANCA-associated vasculitides (AAV). The current addendum provides further recommendations regarding the use of avacopan in AAV based on a review of newly available evidence. METHODS: An updated systematic literature review on avacopan (formerly, CCX168) using Medline, Embase, and the Cochrane Library was performed for publications up to September 2022. New recommendations were developed and categorized according to the EULAR grading levels, as done for previous CanVasc recommendations. A modified Delphi procedure and videoconferences were used to reach ≥80% consensus on the inclusion, wording and grading of each recommendation. RESULTS: Three new recommendations were developed. They focus on avacopan therapy indication and duration, as well as timely glucocorticoid tapering. CONCLUSION: These 2022 addended recommendations provide rheumatologists, nephrologists and other specialists caring for patients with AAV with guidance for the use of avacopan, based on current evidence and consensus from Canadian experts.

Is denosumab associated with an increased risk for infection in patients with low bone mineral density? A systematic review and meta-analysis of randomized controlled trials.

AIM: Denosumab increases bone mineral density through inhibition of the receptor activator of nuclear factor κ-Β ligand (RANKL). RANKL has known immunomodulatory effect. The largest study to date that reviewed denosumab efficacy in osteoporosis demonstrated an increased incidence of serious adverse events of infection (SAEI). We aimed to further evaluate risk of infection and SAEI in denosumab-treated patients. METHOD: PubMed, Embase, Cochrane Central Register of Controlled Trials, and Web of Science were searched for randomized controlled trials. Studies comparing denosumab 60 mg every 6 months with placebo or bisphosphonate for treatment of low bone mineral density were included. Trials were excluded for use of denosumab in cancer patients treated for skeletal-related events, immunosuppressed patient populations, or for comparison to teriparatide. Risk ratios (RR) with a 95% confidence interval (CI) were pooled using a fixed effects model, or a random effects model if heterogeneity occurred. RESULTS: Twenty-four randomized controlled trials (20 470 patients) were analyzed. An increased incidence of any infection (RR 1.11; 95% CI 1.02-1.20; P = 0.02) was observed in denosumab-treated patients compared with bisphosphonates, but not when compared with placebo. In contrast, a higher incidence of SAEI (RR 1.21; 95% CI 1.03-1.43; P = 0.02) was seen with denosumab when compared with placebo, but not compared with bisphosphonates. CONCLUSION: Denosumab-treated patients with low bone mineral density have slightly increased incidence of SAEI compared with placebo, but not when compared with bisphosphonates. Application of these results requires consideration of the entire body of data available regarding denosumab safety.

A case of successful pembrolizumab rechallenge in a patient with non-small-cell lung cancer and grade 3 dermatomyositis.

We report a case of dermatomyositis in a 59-year old female with advanced non-small-cell lung cancer post one cycle of first-line pembrolizumab monotherapy. Her symptoms resolved with high-dose methyl-prednisolone and subsequent prolonged oral prednisone taper over 11 weeks. She achieved durable response over 6 months without further pembrolizumab and was successfully rechallenged without recurrent high-grade immunotoxicity. To our knowledge, this is the only case of severe immune-related dermatomyositis successfully rechallenged with immunotherapy. In this case report, we highlight that dermatomyositis remains a clinical diagnosis with no reliable autoimmune antibody marker. It is a rare immune-related adverse event for which clinicians must remain highly vigilant. We also discuss the rationale and clinical factors to consider on immunotherapy rechallenge decisions.

Double-blind, randomized, placebo-controlled crossover trial of alpha-lipoic acid for the treatment of fibromyalgia pain: the IMPALA trial.

ABSTRACT: Fibromyalgia is a common and challenging chronic pain disorder with few, if any, highly effective and well-tolerated treatments. Alpha-lipoic acid (ALA) is a nonsedating antioxidant with evidence of efficacy in the treatment of symptomatic diabetic neuropathy that has not been evaluated in the setting of fibromyalgia treatment. Thus, we conducted a single-centre, proof-of-concept, randomized, placebo-controlled, crossover trial of ALA for the treatment of fibromyalgia. Twenty-seven participants were recruited, and 24 participants completed both treatment periods of the trial. The median maximal tolerated dose of ALA in this trial was 1663 mg/day. Treatment-emergent adverse events with ALA were infrequent and not statistically different from placebo. For the primary outcome of pain intensity, and for several other validated secondary outcomes, there were no statistically significant differences between placebo and ALA. A post hoc exploratory subgroup analysis showed a significant interaction between gender and treatment with a significant favourable placebo-ALA difference in pain for men, but not for women. Overall, the results of this trial do not provide any evidence to suggest promise for ALA as an effective treatment for fibromyalgia, which is predominantly prevalent in women. This negative clinical trial represents an important step in a collective strategy to identify new, better tolerated and more effective treatments for fibromyalgia.

Vertebral Fractures: Which Radiological Criteria Are Better Associated With the Clinical Course of Osteoporosis?

STUDY PURPOSE: Morphometric methods categorize potential osteoporotic vertebral fractures (OVF) on the basis of loss of vertebral height. A particular example is the widely used semiquantitative morphometric tool proposed by Genant (GSQ). A newer morphologic algorithm-based qualitative (mABQ) tool focuses on vertebral end-plate damage in recognizing OVF. We used data from both sexes in the Canadian Multicentre Osteoporosis Study (CaMos) to compare the 2 methods in identifying OVF at baseline and during 10 years of follow-up. MATERIALS AND METHODS: We obtained lateral thoracic and lumbar spinal radiographs (T4-L4) 3 times, at 5-year intervals, in 828 participants of the population-based CaMos. Logistic regressions were used to study the association of 10-year changes in bone mineral density (BMD) with incident fractures. RESULTS: At baseline, 161 participants had grade 1 and 32 had grade 2 GSQ OVF; over the next 10 years, only 9 of these participants had sustained incident GSQ OVF. Contrastingly, 21 participants at baseline had grade 1 and 48 grade 2 mABQ events; over the next 10 years, 79 subjects experienced incident grade 1 or grade 2 mABQ events. Thus, incident grades 1 and 2 morphologic fractures were 8 times more common than morphometric deformities alone. Each 10-year decrease of 0.01 g/cm2 in total hip BMD was associated with a 4.1% (95% CI: 0.7-7.3) higher odds of having an incident vertebral fracture. CONCLUSIONS: This analysis further suggests that morphometric deformities and morphologic fractures constitute distinct entities; morphologic fractures conform more closely to the expected epidemiology of OVF.

CanVasc Consensus Recommendations for the Management of Antineutrophil Cytoplasm Antibody-associated Vasculitis: 2020 Update.

OBJECTIVE: In 2015, the Canadian Vasculitis Research Network (CanVasc) created recommendations for the management of antineutrophil cytoplasm antibody (ANCA)-associated vasculitides (AAV) in Canada. The current update aims to revise existing recommendations and create additional recommendations, as needed, based on a review of new available evidence. METHODS: A needs assessment survey of CanVasc members informed questions for an updated systematic literature review (publications spanning May 2014 to September 2019) using Medline, Embase, and Cochrane. New and revised recommendations were developed and categorized according to the level of evidence and strength of each recommendation. The CanVasc working group used a 2-step modified Delphi procedure to reach > 80% consensus on the inclusion, wording, and grading of each new and revised recommendation. RESULTS: Eleven new and 16 revised recommendations were created and 12 original (2015) recommendations were retained. New and revised recommendations are discussed in detail within this document. Five original recommendations were removed, of which 4 were incorporated into the explanatory text. The supplementary material for practical use was revised to reflect the updated recommendations. CONCLUSION: The 2020 updated recommendations provide rheumatologists, nephrologists, and other specialists caring for patients with AAV in Canada with new management guidance, based on current evidence and consensus from Canadian experts.

Identifying perceptions and barriers regarding vaccination in patients with rheumatoid arthritis: A Canadian perspective.

AIM: Canadian guidelines recommend that patients with rheumatoid arthritis (RA) receive pneumococcal, influenza and shingles vaccinations. The aim of this study was to identify and understand vaccination rates in Canadian patients with RA. METHODS: We conducted an observational study to evaluate uptake of herpes zoster (HZ), influenza and pneumonia vaccination in a cross-section of patients with RA in Kingston, Ontario, Canada. Data were collected using a self-administered questionnaire in patients attending at an academic rheumatology clinic. If vaccination was not received, the reason was established. RESULTS: Ninety-eight out of a total of 103 patients surveyed met the inclusion criteria and were evaluated: 72.4% had received the influenza vaccination in the past year encompassing a period of 2017-2019. Of the 27.6% who did not, the most common chosen reason was personal preference not to get vaccinated (55.6%). Regarding HZ, 18.4% had received vaccination. Of the 2 available types of vaccines, more participants received Zostavax (66.7%) as compared to Shringrix (33.3%). For those not vaccinated (81.6%), "Other" was the most chosen option (37.5%) with the reasons subsequently specified as cost, concern over interaction with treatment and waiting until age ≥65 years. In terms of pneumococcal vaccination, 36.7% were vaccinated, with the majority being vaccinated with Pneumovax-23 (63.9%) compared to Prevnar-13 (16.7%) or both (19.4%). Of the 63.3% of the participants who did not receive vaccination, the most cited reason was they did not know they should receive pneumococcal vaccination (48.4%). CONCLUSIONS: Vaccination rates among Canadian patients with RA are suboptimal.

Combining Frailty and Trabecular Bone Score Did Not Improve Predictive Accuracy in Risk of Major Osteoporotic Fractures.

It is recognized that the trabecular bone score (TBS) provides skeletal information, and frailty measurement is significantly associated with increased risks of adverse health outcomes. Given the suboptimal predictive power in fracture risk assessment tools, we aimed to evaluate the combination of frailty and TBS regarding predictive accuracy for risk of major osteoporotic fracture (MOF). Data from the prospective longitudinal study of CaMos (Canadian Multicentre Osteoporosis Study) were used for this study. TBS values were estimated using lumbar spine (L1 to L4 ) dual-energy X-ray absorptiometry (DXA) images; frailty was evaluated by a frailty index (FI) of deficit accumulation. Outcome was time to first incident MOF during the follow-up. We used the Harrell's C-index to compare the model predictive accuracy. The Akaike information criterion, likelihood ratio test, and net reclassification improvement (NRI) were used to compare model performances between the model combining frailty and TBS (subsequently called "FI + TBS"), FI-alone, and TBS-alone models. We included 2730 participants (mean age 69 years; 70% women) for analyses (mean follow-up 7.5 years). There were 243 (8.90%) MOFs observed during follow-up. Participants with MOF had significantly higher FI (0.24 versus 0.20) and lower TBS (1.231 versus 1.285) than those without MOF. FI and TBS were significantly related with MOF risk in the model adjusted for FRAX with bone mineral density (BMD) and other covariates: hazard ratio (HR) = 1.26 (95% confidence interval [CI] 1.11-1.43) for per-SD increase in FI; HR = 1.38 (95% CI 1.21-1.59) for per-SD decrease in TBS; and these associations showed negligible attenuation (HR = 1.24 for per-SD increase in FI, and 1.35 for per-SD decrease in TBS) when combined in the same model. Although the model FI + TBS was a better fit to the data than FI-alone and TBS-alone, only minimal and nonsignificant enhancement of discrimination and NRI were observed in FI + TBS. To conclude, frailty and TBS are significantly and independently related to MOF risk. Larger studies are warranted to determine whether combining frailty and TBS can yield improved predictive accuracy for MOF risk. © 2020 American Society for Bone and Mineral Research.

Post-Streptococcal Reactive Arthritis.

INTRODUCTION: Post-Streptococcal Reactive Arthritis (PSRA) is defined as inflammatory arthritis of ≥1 joint associated with a recent group A streptococcal infection in a patient who does not fulfill the Jones criteria for the diagnosis of Acute Rheumatic Fever (ARF). METHODS: In this narrative review, we conducted a systematic search on MEDLINE, EMBASE, Cochrane Library and Google Scholar using the words poststreptococcal reactive arthritis. The search covered the time period between 1982 and 2016. The purpose of this review is to summarize the current state of knowledge of PSRA with respect to the definition, epidemiology, clinical presentation and treatment. We also summarize the key differences between PSRA, reactive arthritis (ReA) and ARF. RESULTS: PSRA has a bimodal age distribution at ages 8-14 and 21-37 years with an almost equal male to female ratio. Clinically, it causes acute asymmetrical non-migratory polyarthritis, however, tenosynovitis and small joint arthritis may occur. This disease entity can be associated with extraarticular manifestations, including erythema nodosum, uveitis and glomerulonephritis. The frequency of HLA-B27 in PSRA does not differ from that of the normal population, which suggests that it is a separate entity from ReA. Involvement of the axial skeleton, including sacroiliitis, is uncommon in PSRA. PSRA tends to occur within 10 days of a group A streptococcal infection, as opposed to the 2 to 3 weeks delay for ARF. PSRA can be associated with prolonged or recurrent arthritis, in contrast to ARF, in which arthritis usually lasts a few days to 3 weeks. Treatment usually involves NSAIDs or corticosteroids. CONCLUSION: We summarize clinical features that help differentiate PSRA from ARF and ReA. First-line treatment options include NSAIDs and corticosteroids. Most cases resolve spontaneously within a few weeks, but some cases are recurrent or prolonged. There are no published randomized controlled trials of PSRA.

Is Rheumatoid Arthritis a Risk Factor for Fractures: A Systematic Review of Observational Studies.

AIM: The primary objective was to assess the risk of fractures in adults with RA compared with controls from the general population. The review also assessed an increased risk of fractures in RA patients when accounting for steroid use, RA disease severity or functional impairment. METHODS: Citations were screened from MEDLINE, EMBASE, Cochrane Database of Systematic Reviews and CINAHL. Included citations were written in English, including adult patients at least 18 years of age and compared fracture incidence or prevalence between RA patients and a control group. Case-control, cohort and cross-sectional studies were included. RESULTS: There were a total of 3451 citations; after application of the inclusion criteria, 17 studies were selected. In 14 of the 17 studies, there was an increase in the risk of fracture in RA patients compared to controls. In studies that evaluated for glucocorticoid use, four of 13 demonstrated an increased risk of fracture with glucocorticoid use, however, only two of these four studies specifically assessed glucocorticoid use amongst patients with RA. In studies that analyzed RA severity or functional impairment, two of seven demonstrated disease severity or impairment as a risk factor for fracture. There was marked study heterogeneity in terms of patient and fracture characteristics, which was a limitation of the analysis that impeded the ability to make direct comparisons. CONCLUSION: The risk of fracture in RA patients is elevated when compared to the general population, although the etiology of the increased risk remains to be elucidated.

Predictors of imminent non-vertebral fracture in elderly women with osteoporosis, low bone mass, or a history of fracture, based on data from the population-based Canadian Multicentre Osteoporosis Study (CaMos).

Using data from the Canadian Multicentre Osteoporosis Study, several risk factors predictive of imminent (2-year) risk of low-trauma non-vertebral fracture among high-risk women were identified, including history of falls, history of low-trauma fracture, poorer physical function, and lower T score. Careful consideration should be given to targeting this population for therapy. PURPOSE: Fracture risk assessment has focused on a long-term horizon and populations with a broad risk range. For elderly women with osteoporosis or low bone mass, or a history of fragility fractures ("high-risk women"), risk prediction over a shorter horizon may have greater clinical relevance. METHODS: A repeated-observations design and data from the Canadian Multicentre Osteoporosis Study were employed. Study population comprised women aged ≥ 65 years with T score (total hip, femoral neck, spine) ≤ - 1.0 or prior fracture. Hazard ratios (HR) for predictors of low-trauma non-vertebral fracture during 2-year follow-up were estimated using multivariable shared frailty model. RESULTS: The study population included 3228 women who contributed 5004 observations; 4.8% experienced low-trauma non-vertebral fracture during the 2-year follow-up. In bivariate analyses, important risk factors included age, back pain, history of falls, history of low-trauma fracture, physical function, health status, and total hip T score. In multivariable analyses, only four independent predictors were identified: falls in past 12 months (≥ 2 falls: HR = 1.9; 1 fall: HR = 1.5), low-trauma fracture in past 12 months (≥ 1 fracture: HR = 1.7), SF-36 physical component summary score (≤ 42.0: HR = 1.6), and total hip T score (≤ - 3.5: HR = 3.7; > - 3.5 to ≤ - 2.5: HR = 2.5; > - 2.5 to ≤ - 1: HR = 1.3). CONCLUSIONS: Imminent risk of low-trauma non-vertebral fracture is elevated among high-risk women with a history of falls or low-trauma fracture, poorer physical function, and lower T score. Careful consideration should be given to identifying and targeting this population for therapy.

Frailty and Risk of Fractures in Patients With Type 2 Diabetes.

OBJECTIVE: We aimed to explore whether frailty was associated with fracture risk and whether frailty could modify the propensity of type 2 diabetes toward increased risk of fractures. RESEARCH DESIGN AND METHODS: Data were from a prospective cohort study. Our primary outcome was time to the first incident clinical fragility fracture; secondary outcomes included time to hip fracture and to clinical spine fracture. Frailty status was measured by a Frailty Index (FI) of deficit accumulation. The Cox model incorporating an interaction term (frailty × diabetes) was used for analyses. RESULTS: The analysis included 3,149 (70% women) participants; 138 (60% women) had diabetes. Higher bone mineral density and FI were observed in participants with diabetes compared with control subjects. A significant relationship between the FI and the risk of incident fragility fractures was found, with a hazard ratio (HR) of 1.02 (95% CI 1.01-1.03) and 1.19 (95% CI 1.10-1.33) for per-0.01 and per-0.10 FI increase, respectively. The interaction was also statistically significant (P = 0.018). The HR for per-0.1 increase in the FI was 1.33 for participants with diabetes and 1.19 for those without diabetes if combining the estimate for the FI itself with the estimate from the interaction term. No evidence of interaction between frailty and diabetes was found for risk of hip and clinical spine fractures. CONCLUSIONS: Participants with type 2 diabetes were significantly frailer than individuals without diabetes. Frailty increases the risk of fragility fracture and enhances the effect of diabetes on fragility fractures. Particular attention should be paid to diabetes as a risk factor for fragility fractures in those who are frail.

The Ottawa Panel guidelines on programmes involving therapeutic exercise for the management of hand osteoarthritis.

OBJECTIVE:: To identify programmes involving therapeutic exercise that are effective for the management of hand osteoarthritis and to provide stakeholders with updated, moderate to high-quality recommendations supporting exercises for hand osteoarthritis. METHODS:: A systematic search and adapted selection criteria included comparable trials with exercise programmes for managing hand osteoarthritis. Based on the evaluated evidence, a panel of experts reached consensus through a Delphi approach endorsing the recommendations. A hierarchical alphabetical grading system (A, B, C+, C, C-, D-, D, D+, E, F) was based on clinical importance (≥15%) and statistical significance ( P < 0.05). RESULTS:: Ten moderate- to high-quality studies were included. Eight studies with programmes involving therapeutic exercise (e.g. range of motion (ROM) + isotonic + isometric + functional exercise) seemed to be effective. Forty-six positive grade recommendations (i.e. A, B, C+) were obtained during short-term (<12 weeks) trials for pain, stiffness, physical function, grip strength, pinch strength, range of motion, global assessment, pressure pain threshold, fatigue and abductor pollicis longus moment and during long-term (>12 weeks) trials for physical function and pinch strength. CONCLUSION:: Despite that many programmes involving exercise with positive recommendations for clinical outcomes are available to healthcare professionals and hand osteoarthritis patients that aid in the management of hand osteoarthritis, there is a need for further research to isolate the specific effect of exercise components.

Adult Premenopausal Bone Health Related to Reproductive Characteristics-Population-Based Data from the Canadian Multicentre Osteoporosis Study (CaMos).

Amenorrhea is important for women's bone health. However, few have reported reproductive, anthropometric (body mass index [BMI], height) and bone health (areal bone mineral density [BMD], prevalent fractures) in a population-based study. The purposes of this cross-sectional study of women in the randomly-selected Canadian Multicentre Osteoporosis Study (CaMos) population were: (1) to describe reproductive, demographic, anthropometric and lifestyle variables; and (2) in menstruating women, to relate reproductive and other variables to BMD at the lumbar spine (L1-4, LS), femoral neck (FN) and total hip (TH) sites and to prevalent fragility fractures. This study describes the reproductive characteristics of 1532 women aged 30⁻60 years. BMD relationships with reproductive and other variables were described in the 499 menstruating women. Mean menarche age was 12.8 years, 96% of women were parous and 95% had used combined hormonal contraceptives (CHC). Infertility was reported by 9%, androgen excess by 13%, amenorrhea by 8% and nulliparity by 4%. LS BMD was negatively associated with amenorrhea and androgen excess and positively related to current BMI and height. A later age at menarche negatively related to FN BMD. BMI and height were strongly related to BMD at all sites. Prevalent fragility fractures were significantly associated with quartiles of both LS and TH BMD.

Comparative Analysis of the Radiology of Osteoporotic Vertebral Fractures in Women and Men: Cross-Sectional and Longitudinal Observations from the Canadian Multicentre Osteoporosis Study (CaMos).

We compared two methods for osteoporotic vertebral fracture (VF) assessment on lateral spine radiographs, the Genant semiquantitative (GSQ) technique and a modified algorithm-based qualitative (mABQ) approach. We evaluated 4465 women and 1771 men aged ≥50 years from the Canadian Multicentre Osteoporosis Study with available X-ray images at baseline. Observer agreement was lowest for grade 1 VFs determined by GSQ. Among physician readers, agreement was greater for VFs diagnosed by mABQ (ranging from 0.62 [95% confidence interval (CI) 0.00-1.00] to 0.88 [0.76-1.00]) than by GSQ (ranging from 0.38 [0.17-0.60] to 0.69 [0.54-0.85]). GSQ VF prevalence (16.4% [95% CI 15.4-17.4]) and incidence (10.2/1000 person-years [9.2; 11.2]) were higher than with the mABQ method (prevalence 6.7% [6.1-7.4] and incidence 6.3/1000 person-years [5.5-7.1]). Women had more prevalent and incident VFs relative to men as defined by mABQ but not as defined by GSQ. Prevalent GSQ VFs were predominantly found in the mid-thoracic spine, whereas prevalent mABQ and incident VFs by both methods co-localized to the junction of the thoracic and lumbar spine. Prevalent mABQ VFs compared with GSQ VFs were more highly associated with reduced adjusted L1 to L4 bone mineral density (BMD) (-0.065 g/cm2 [-0.087 to -0.042]), femoral neck BMD (-0.051 g/cm2 [-0.065 to -0.036]), and total hip BMD (-0.059 g/cm2 [-0.076 to -0.041]). Prevalent mABQ VFs compared with prevalent GSQ were also more highly associated with incident VF by GSQ (odds ratio [OR] = 3.3 [2.2-5.0]), incident VF by mABQ (9.0 [5.3-15.3]), and incident non-vertebral major osteoporotic fractures (1.9 [1.2-3.0]). Grade 1 mABQ VFs, but not grade 1 GSQ VFs, were associated with incident non-vertebral major osteoporotic fractures (OR = 3.0 [1.4-6.5]). We conclude that defining VF by mABQ is preferred to the use of GSQ for clinical assessments. © 2017 American Society for Bone and Mineral Research.