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ObjectiveThe objective is to update recommendations for prevention and treatment of glucocorticoid-induced osteoporosis (GIOP) for patients with rheumatic or nonrheumatic conditions receiving >3 months treatment with glucocorticoids (GCs) ≥2.5 mg daily.MethodsAn updated systematic literature review was performed for clinical questions on nonpharmacologic, pharmacologic treatments, discontinuation of medications, and sequential therapy. Grading of Recommendations Assessment, Development and Evaluation approach was used to rate the certainty of evidence. A Voting Panel achieved ≥70% consensus on the direction (for or against) and strength (strong or conditional) of recommendations.ResultsFor adults beginning or continuing >3 months of GC treatment, we strongly recommend as soon as possible after initiation of GCs, initial assessment of fracture risks with clinical fracture assessment, bone mineral density with vertebral fracture assessment or spinal x-ray, and Fracture Risk Assessment Tool if ≥40 years old. For adults at medium, high, or very high fracture risk, we strongly recommend pharmacologic treatment. Choice of oral or intravenous bisphosphonates, denosumab, or parathyroid hormone analogs should be made by shared decision-making. Anabolic agents are conditionally recommended as initial therapy for those with high and very high fracture risk. Recommendations are made for special populations, including children, people with organ transplants, people who may become pregnant, and people receiving very high-dose GC treatment. New recommendations for both discontinuation of osteoporosis therapy and sequential therapies are included.ConclusionThis guideline provides direction for clinicians and patients making treatment decisions for management of GIOP. These recommendations should not be used to limit or deny access to therapies.

ObjectiveTo assess the effects of weight loss and weight gain on hip and knee radiographic changes, pain, and joint replacement over 4 years.MethodsParticipants (n = 2,752) from the Osteoarthritis Initiative were classified as those with weight gain (more than 5% gain), weight loss (more than -5% loss), or as controls (-3% to 3% change) over 4 years. Generalized estimating equations (adjusted for age, sex, and body mass index) were used to assess the relationship between the weight-change group and 4-year changes in knee radiographic osteoarthritis (OA) (Kellgren/Lawrence [K/L] grade), hip OA (Croft summary grade), joint space narrowing (JSN), and joint pain.ResultsFor radiographic knee OA, weight loss was associated with significantly lower odds of K/L grade worsening over 4 years (odds ratio [OR] 0.69 [95% confidence interval (95% CI) 0.53-0.91], P = 0.009), and weight gain was significantly associated with higher odds of medial knee JSN (OR 1.29 [95% CI 1.01-1.64], P = 0.038) compared to controls. For knee pain, weight loss was significantly associated with knee pain resolution over 4 years (OR 1.40 [95% CI 1.06-1.86], P = 0.019) while weight gain was associated with knee pain development (OR 1.34 [95% CI 1.08-1.67], P = 0.009) compared to controls. For all hip outcomes, no significant associations (P > 0.05) were found with weight-change groups. The associations between the weight-change group and total hip or total knee replacement were not significant (P > 0.05).ConclusionThis large, longitudinal study (n = 2,752 with 4-year follow-up) suggests that weight loss may protect against, and weight gain may exacerbate, radiographic and symptomatic knee OA, while weight change (at a 5% threshold) does not have significant effects on hip OA.

ObjectiveTo assess the relation of symptomatic knee osteoarthritis (OA), knee pain, and radiographic knee OA to All-cause mortality and to identify mediators in the causal pathway.MethodsParticipants from the Osteoarthritis Initiative were divided into 4 groups: 1) symptomatic knee OA (i.e., both radiographic knee OA [Kellgren/Lawrence grade ≥2] and knee pain); 2) knee pain only; 3) radiographic knee OA only; and 4) neither radiographic knee OA nor knee pain. We examined the relation of knee OA status to All-cause mortality using a multivariable Cox proportional hazards model and assessed the extent to which the association was mediated by disability, physical component summary (PCS) and mental component summary (MCS) scores for quality of life (QoL), and use of oral pain-relief medications (i.e., nonsteroidal antiinflammatory drugs and opioids).ResultsAmong 4,796 participants, 282 died over the 96-month follow-up period. Compared with those with neither radiographic knee OA nor knee pain, multivariable-adjusted hazard ratios (HRs) of mortality were 2.2 (95% confidence interval [95% CI] 1.6-3.1) for symptomatic knee OA, 0.9 (95% CI 0.6-1.4) for knee pain only, and 2.0 (95% CI 1.4-2.9) for radiographic knee OA only, respectively. Indirect effects (HRs) of symptomatic knee OA on mortality via disability and PCS of QoL were 1.1 (95% CI 1.0-1.4) and 1.2 (95% CI 1.0-1.4), respectively. No apparent mediation effect was observed through either MCS of QoL or oral pain-relief medications use.ConclusionParticipants with either symptomatic or radiographic knee OA were at an increased risk of All-cause mortality. Increased risk of mortality from symptomatic knee OA was partially mediated through its effect on disability and PCS of QoL.

ObjectiveTo determine the cross-sectional and longitudinal associations of vitamin C and D intake with magnetic resonance imaging (MRI) measures of cartilage composition (T2) and joint structure (cartilage, meniscus, and bone marrow) using data from the Osteoarthritis Initiative (OAI) cohort.MethodsA total of 1,785 subjects with radiographic Kellgren/Lawrence knee grades 0-3 in the right knee were selected from the OAI database. Vitamins C and vitamin D intake (diet, supplements, and total) were assessed using the Block Brief 2000 Food Frequency Questionnaire at baseline. The MRI analysis protocol included 3T cartilage T2 quantification and semiquantitative joint morphology gradings (Whole-Organ Magnetic Resonance Imaging Score [WORMS]) at baseline and 4 years. Linear regression was used to assess the association between standardized baseline vitamin intake and both baseline WORMS scores and standardized cartilage T2 values.ResultsHigher vitamin C intake was associated with lower average cartilage T2 values, medial tibia T2 values, and medial tibia WORMS scores (standardized coefficient range -0.07 to -0.05, P < 0.05). Higher vitamin D intake was associated with a lower cartilage WORMS sum score and medial femur WORMS score (standardized coefficient range -0.24 to -0.09, P < 0.05). Consistent use of vitamin D supplements of 400 IU at least once a week over 4 years was associated with significantly less worsening of cartilage, meniscus, and bone marrow abnormalities (odds ratio range 0.40-0.56, P < 0.05).ConclusionSupplementation with vitamin D over 4 years was associated with significantly less progression of knee joint abnormalities. Given the observational nature of this study, future longitudinal randomized controlled trials of vitamin D supplementation are warranted.

ObjectiveTo examine the associations of prevalent arthritis with systemic inflammation in older men and to test whether sleep health mediates the associations.MethodsCross-sectional data came from 2,562 community-dwelling older men (all were age 65 years or older; mean age 76 years) in the Osteoporotic Fractures in Men Study who participated in a sleep ancillary study in 2003-2005. Participants were classified as having osteoarthritis (OA) (24%) or rheumatoid arthritis (RA) (0.7%) based on self-reported diagnoses and medication use. We constructed a composite score of multidimensional sleep health (i.e., perceived sleep quality, sleepiness, frequency of daytime napping, wake after sleep onset, and sleep duration) measured by both self-report and actigraphy. We also created binary indicators of elevated inflammation using C-reactive protein (CRP) (>3 mg/liter) and interleukin-6 (IL-6) (>1.08 pg/ml) levels. Analyses controlled for age, diagnosed sleep disorders, body mass index, smoking status, relevant medication use, and comorbidities.ResultsOlder men with OA did not have higher risk of elevated CRP or IL-6 levels. However, indirect associations of OA through sleep health were found. OA was associated with poorer sleep health, which was further associated with 16% higher odds of elevated CRP (P < 0.001) and 12% higher odds of elevated IL-6 (P < 0.01) levels after controlling for OA. Older men with RA had higher odds of elevated CRP and IL-6 levels, but the associations were not mediated by sleep health.ConclusionFindings suggest that promoting sleep health may help reduce the risk of systemic inflammation in older men with OA.

ObjectiveThe association of diabetes mellitus (DM) with increased risk of knee osteoarthritis (OA) is uncertain. We evaluated associations of DM and biomarkers of abnormal glucose metabolism with incident radiographic knee OA, controlling for body mass index (BMI).MethodsParticipants (mean ± SD age 60.6 ± 7.8 years; mean ± SD body mass index [BMI] 29.1 ± 4.9 kg/m2 ) were from the Multicenter Osteoarthritis Study and did not have radiographic knee OA at baseline (Kellgren/Lawrence [K/L] grade

ObjectiveTo develop recommendations for prevention and treatment of glucocorticoid-induced osteoporosis (GIOP).MethodsWe conducted a systematic review to synthesize the evidence for the benefits and harms of GIOP prevention and treatment options. The Grading of Recommendations Assessment, Development and Evaluation methodology was used to rate the quality of evidence. We used a group consensus process to determine the final recommendations and grade their strength. The guideline addresses initial assessment and reassessment in patients beginning or continuing long-term (≥3 months) glucocorticoid (GC) treatment, as well as the relative benefits and harms of lifestyle modification and of calcium, vitamin D, bisphosphonate, raloxifene, teriparatide, and denosumab treatment in the general adult population receiving long-term GC treatment, as well as in special populations of long-term GC users.ResultsBecause of limited evidence regarding the benefits and harms of interventions in GC users, most recommendations in this guideline are conditional (uncertain balance between benefits and harms). Recommendations include treating only with calcium and vitamin D in adults at low fracture risk, treating with calcium and vitamin D plus an additional osteoporosis medication (oral bisphosphonate preferred) in adults at moderate-to-high fracture risk, continuing calcium plus vitamin D but switching from an oral bisphosphonate to another antifracture medication in adults in whom oral bisphosphonate treatment is not appropriate, and continuing oral bisphosphonate treatment or switching to another antifracture medication in adults who complete a planned oral bisphosphonate regimen but continue to receive GC treatment. Recommendations for special populations, including children, people with organ transplants, women of childbearing potential, and people receiving very high-dose GC treatment, are also made.ConclusionThis guideline provides direction for clinicians and patients making treatment decisions. Clinicians and patients should use a shared decision-making process that accounts for patients' values, preferences, and comorbidities. These recommendations should not be used to limit or deny access to therapies.

ObjectiveTo investigate cross-sectional and longitudinal associations of diffuse idiopathic skeletal hyperostosis (DISH) and thoracic kyphosis in older persons.MethodsDISH and kyphosis were assessed in 1,500 men from the Osteoporotic Fractures in Men (MrOS) study and in 1,267 women from the Study of Osteoporotic Fractures (SOF). DISH was assessed using baseline lateral spine radiographs, and Cobb angle of kyphosis was measured from baseline and followup radiographs, a mean 4.6 years later in men, and 3.7 and 15 years later in women. Linear regression was used to analyze associations of DISH with baseline Cobb angle and with percent annualized change in Cobb angle. We tested for heterogeneity among studies.ResultsDISH was identified in 222 participants in MrOS (15%) and in 156 participants in SOF (12%). Participants with DISH in both cohorts had higher baseline Cobb angles (P  0.05) for men or women. Women with DISH had less kyphosis progression over 15 years (0.25% less annualized change in Cobb) than those without DISH.ConclusionPrevalent DISH is associated with greater kyphosis in older men and women, and is not significantly associated with a change in kyphosis over 4-5 years. However, in women followed over 15 years, DISH was associated with less progression of kyphosis. These results suggest that DISH influences kyphosis and may slow progression over the long term. Additional studies of DISH/kyphosis associations are warranted to understand the functional implications of this finding.

ObjectiveTo investigate hip shape by active shape modeling (ASM) as a potential predictor of incident radiographic hip osteoarthritis (RHOA) and symptomatic hip osteoarthritis (SRHOA).MethodsAll hips developing RHOA from baseline (Kellgren/Lawrence [K/L] grade 0/1) to mean 6-year followup (K/L grade ≥2, 190 hips) and 1:1 control hips (K/L grade 0/1 at both times, 192 hips) were included. Proximal femur shape was defined on baseline anteroposterior pelvis radiographs and submitted to ASM, producing a mean shape and continuous variables representing independent modes of shape variation. Mode scores (n = 14, explaining 95% of shape variance) were simultaneously included in logistic regression models with incident RHOA and SRHOA as dependent variables, adjusted for intraperson correlations, sex, race, body mass index (BMI), baseline K/L grade, and/or symptoms.ResultsWe evaluated 382 hips from 342 individuals: 61% women and 83% white, with mean age 62 years and mean BMI 29 kg/m(2) . Several modes differed by sex and race, but no modes were associated with incident RHOA overall. Among men only, modes 1 and 2 were significantly associated (for a 1-SD decrease in mode 1 score: odds ratio [OR] 1.7 [95% confidence interval (95% CI) 1.1-2.5] and for a 1-SD increase in mode 2 score: OR 1.5 [95% CI 1.0-2.2]) with incident RHOA. A 1-SD decrease in mode 2 or 3 score increased the odds of SRHOA by 50%.ConclusionThis study confirms other reports that variations in proximal femur shape have a modest association with incident hip OA. The observation of proximal femur shape associations with hip symptoms requires further investigation.

ObjectiveWe conducted a cross-sectional study to describe the prevalence of tibiofemoral joint space narrowing (JSN) in medial and lateral compartments and assess whether it differs by sex and ethnic groups, and, if it does, to what extent such a difference is accounted for by knee malalignment.MethodsThe Multicenter Osteoarthritis Study is an observational study of persons ages 50-79 years with either symptomatic knee osteoarthritis or high risk of disease. Knee radiographs were assessed for JSN in each tibiofemoral compartment. Mechanical axis angle was measured using full-extremity films. We compared the proportion of knees with medial compartment JSN and with lateral JSN between men and women, as well as between whites and African Americans, using a logistic regression model adjusting for covariates (race or sex and body mass index, age, education, and clinic site). We used generalized estimating equations to account for correlation between 2 knees within a person.ResultsOf 5,202 knees (2,652 subjects), 1,532 (29.5%) had medial JSN and 427 (8.2%) had lateral JSN. Lateral JSN was more prevalent in the knees of women than in men (odds ratio [OR] 1.9, 95% confidence interval [95% CI] 1.5-2.4) and was also higher in the knees of African Americans than in whites (OR 2.4, 95% CI 1.7-3.3). Further adjustment for malalignment attenuated the OR for sex but not the OR for race.ConclusionWomen and African Americans are more likely to have lateral JSN than men and whites, respectively. Valgus malalignment may contribute to the higher prevalence in women.

Objective: To evaluate sleep quality in women with hip pain due to daily activities involving the lower extremity joints.Methods: We evaluated the association of the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) hip pain severity score with objective sleep measures obtained by wrist actigraphy in 2,225 white women ≥ 65 years of age enrolled in the Study of Osteoporotic Fractures.Results: Women had an increased odds of spending ≥ 90 minutes awake after sleep onset (odds ratio [OR] 1.28, 95% confidence interval [95% CI] 1.11-1.50) for every 5-point increase in hip pain score after adjustment for all covariates. Hip pain when sitting or lying was the strongest predictor of sleep fragmentation (OR 2.0, 95% CI 1.47-2.73); however, standing pain was associated with a higher number of awake minutes in bed scored from sleep onset to the end of the last sleep episode, independent of pain while in bed (OR 1.41, 95% CI 1.07-2.01). Sleep disturbances increased significantly after the first 2 hours of sleep in women with severe hip pain compared to those without hip pain (mean ± SD 1.4 ± 0.47 minutes per hour of sleep; P < 0.003). Similar associations were observed for long wake episodes >5 minutes. There were no associations between daytime napping, sleep latency, sleep efficiency, and total sleep minutes and WOMAC hip pain.Conclusion: Fragmented sleep was greater in women with hip pain compared to those without hip pain; however, fragmented sleep in women with severe hip pain compared to those without hip pain was unchanged until after the first 2 hours of sleep. Further investigations into pain medications wearing off over time or the prolonged periods of inactivity decreasing the pain threshold are warranted. [ABSTRACT FROM AUTHOR]