Predictors of lower extremity fracture-related amputation in persons with traumatic spinal cord injury: a case-control study.

STUDY DESIGN: This is a retrospective case-control study. OBJECTIVES: To identify predictors of lower extremity (LE) long bone fracture-related amputation in persons with traumatic spinal cord injury (tSCI). SETTING: US Veterans Health Administration facilities (2005-2015). METHODS: Fracture-amputation sets in Veterans with tSCI were considered for inclusion if medical coding indicated a LE amputation within 365 days following an incident LE fracture. The authors adjudicated each fracture-amputation set by electronic health record review. Controls with incident LE fracture and no subsequent amputation were matched 1:1 with fracture-amputation sets on site and date of fracture (±30 days). Multivariable conditional logistic regression determined odds ratios (OR) and 95% confidence intervals (CI) for potential predictors (motor-complete injury; diabetes mellitus (DM); peripheral vascular disease (PVD); smoking; primary (within 30 days) nonsurgical fracture management; pressure injury and/or infection), controlling for age and race. RESULTS: Forty fracture-amputation sets from 37 Veterans with LE amputations and 40 unique controls were identified. DM (OR = 26; 95% CI, 1.7-382), PVD (OR = 30; 95% CI, 2.5-371), and primary nonsurgical management (OR = 40; 95% CI, 1.5-1,116) were independent predictors of LE fracture-related amputation. CONCLUSIONS: Early and aggressive strategies to prevent DM and PVD in tSCI are needed, as these comorbidities are associated with increased odds of LE fracture-related amputation. Nonsurgical fracture management increased the odds of LE amputation by at least 50%. Further large, prospective studies of fracture management in tSCI are needed to confirm our findings. Physicians and patients should consider the potential increased risk of amputation associated with non-operative management of LE fractures in shared decision making.

Lower extremity fracture prevention and management in persons with spinal cord injuries and disorders: The patient perspective.

CONTEXT/OBJECTIVE: To describe patient experiences with fracture prevention and management among persons with spinal cord injuries/disorders (SCI/D). DESIGN: Qualitative data collected via semi-structured telephone interviews. SETTING: Veterans Health Administration (VA) SCI/D System of Care. PARTICIPANTS: Veterans with SCI/D (n = 32) who had experienced at least one lower-extremity fracture in the prior 18 months. INTERVENTIONS: N/A. OUTCOME MEASURES: Interview questions addressed patients': pre-fracture knowledge of osteoporosis and bone health, diagnosis and management of osteoporosis, history and experiences with fracture treatment, and post-fracture care and experiences. RESULTS: Participants expressed concerns about bone health and fractures in particular, which for some, limited activities and participation. Participants recalled receiving little information from providers about bone health or osteoporosis and described little knowledge about osteoporosis prevention prior to their fracture. Few participants reported medication management for osteoporosis, however many reported receiving radiographs/scans to confirm a fracture and most reported being managed non-operatively. Some reported preference for surgical treatment and believed their outcomes would have been better had their fracture been managed differently. Many reported not feeling fully included in treatment decision-making. Some described decreased function, independence and/or participation post-fracture. CONCLUSION(S): Our results indicate that persons with SCI/D report lacking substantive knowledge about bone health and/or fracture prevention, and following fracture, feel unable and/or hesitant to resume pre-fracture participation. In addition, our findings indicate that individuals with SCI/D may not feel as engaged as they would like to be in establishing fracture treatment plans. As such, persons with SCI/D may benefit from ongoing discussions with providers about risks and benefits of fracture treatment options and consideration of subsequent function and participation, to ensure patients preferences are considered.

Estimating 24-Hour Urinary Excretion of Sodium and Potassium Is More Reliable from 24-Hour Urine Than Spot Urine Sample in a Feeding Study of US Older Postmenopausal Women.

BACKGROUND: Assessing estimated sodium (Na) and potassium (K) intakes derived from 24-h urinary excretions compared with a spot urine sample, if comparable, could reduce participant burden in epidemiologic and clinical studies. OBJECTIVES: In a 2-week controlled-feeding study, Na and K excretions from a 24-h urine collection were compared with a first-void spot urine sample, applying established algorithms and enhanced models to estimate 24-h excretion. Actual and estimated 24-h excretions were evaluated relative to mean daily Na and K intakes in the feeding study. METHODS: A total of 153 older postmenopausal women ages 75.4 ± 3.5 y participated in a 2-wk controlled-feeding study with a 4-d repeating menu cycle based on their usual intake (ClinicalTrials.gov Identifier: NCT00000611). Of the 150 participants who provided both a first-void spot urine sample and a 24-h urine collection on the penultimate study day, statistical methods included Pearson correlations for Na and K between intake, 24-h collections, and the 24-h estimated excretions using 4 established algorithms: enhanced biomarker models by regressing ln-transformed intakes on ln-transformed 24-h excretions or ln-transformed 24-h estimated excretions plus participant characteristics and sensitivity analyses for factors potentially influencing Na or K excretion (e.g., possible kidney disease estimated glomerular filtration rate <60 mL/min/1.73 m2 ). RESULTS: Pearson correlation coefficients between Na and K intakes and actual 24-h excretions were 0.57 and 0.38-0.44 for estimated 24-h excretions, depending on electrolyte and algorithm used. Enhanced biomarker model cross-validated R 2 (CVR2) for 24-h excretions were 38.5% (Na), 40.2% (K), and 42.0% (Na/K). After excluding participants with possible kidney disease, the CVR2 values were 43.2% (Na), 40.2% (K), and 38.1% (Na/K). CONCLUSIONS: Twenty-four-hour urine excretion measurement performs better than estimated 24-h excretion from a spot urine as a biomarker for Na and K intake among a sample of primarily White postmenopausal women.

Treatment of Lower Extremity Fractures in Chronic Spinal Cord Injury: A Systematic Review of the Literature.

OBJECTIVE: To review the literature regarding outcomes of surgical and nonsurgical management of lower extremity (LE) fractures in chronic spinal cord injury (SCI). TYPE: Systematic review. LITERATURE SURVEY: Medline (PubMed), Embase, Cochrane Database of Systemic Reviews, Cochrane Central, Cumulative Index to Nursing and Allied Health Literature, ClinicalTrials.gov, International Clinical Trials Registry Platform, and International Standard Randomized Controlled Trials were searched from January 1, 1966, to March 1, 2019. METHODOLOGY: Search was restricted to English language and adults (age ≥ 18 yr). Titles and abstracts were reviewed for relevance to study topics for inclusion. Case reports, reviews, non-SCI population studies, and studies examining fractures at the time of acute SCI were excluded. References of included articles from the original search and task force and external submissions yielded two additional articles that were included in the review after voting by task force members. Data extraction was performed by four task force members using a data extraction form, glossary, and instructions created in Microsoft Excel. Quality assessment was performed by three methodologists using prespecified criteria. SYNTHESIS: Twenty-three articles were included. Use of surgery to treat LE fractures in chronic SCI has increased, though nonoperative management was still more frequently reported. Regardless of type of management, amputations, nonunion/malunion, and pressure injuries were among the most commonly reported complications. Functional and quality of life outcomes were less frequently reported. CONCLUSIONS: There is insufficient evidence to support operative versus nonoperative management as best practice for management of LE fracture of SCI. Existing literature was limited by small sample sizes, lack of randomization or matched study designs, significant heterogeneity in populations and treatment strategies studied, and variability in defining and reporting outcomes of interest. The field would benefit from future research to address study design issues and standardization of outcome reporting to facilitate comparison of outcomes of operative versus nonoperative management.

Reasons for Initiation and Discontinuation of Pharmacological Therapies for Osteoporosis in Veterans with Spinal Cord Injury and Disorders.

INTRODUCTION: Medications for osteoporosis have not been reported to reduce fracture rates in patients with spinal cord injury and disorders (SCI/D), yet these medications are still prescribed. Clinical decision-making underscoring the initiation and discontinuation of osteoporosis medications in SCI/D remains poorly understood. METHODOLOGY: Veterans with a SCI/D with at least one prescription for an osteoporosis medication (bisphosphonate, calcitonin, denosumab, raloxifene, and teriparatide) who received healthcare within Veterans Affairs (VA) from 2005 to 2015 were identified using VA administrative databases. A 10% subsample of Veterans was selected for electronic health record review. RESULTS: Two hundred and sixty-seven Veterans with 330 prescriptions underwent electronic health record review. Bisphosphonates were the most frequently prescribed medication for osteoporosis (n = 223, 67.6%). Of the 187 Veterans with prescriptions for prevention or treatment of osteoporosis, the primary reason for initiation was Dual Energy X-ray Absorptiometry (DXA) scan with osteopenia or osteoporosis (n = 119, 63.6% of Veterans), primarily at the hip (81.0% of DXAs). The majority (79.0%) of DXAs were "screening tests," with SCI/D being the sole reason for the scan. Fractures (n = 51, 27.3%) and fall risk concerns (n = 29, 15.5%) were other major reasons for initiation. On average, oral bisphosphonates were filled for <3 yr, with medication-related side effects (n = 23, 15.8% of bisphosphonates discontinued), predominately gastrointestinal (n = 17, 73.9% of reported side effects), the most common reason for discontinuation. Drug holidays occurred in 14.3% of 35 oral bisphosphonates used for ≥5 yr. No cases of osteonecrosis of the jaw were found. There was one case of an atypical femoral fracture which could not be confirmed. CONCLUSIONS: The decision to initiate pharmacological therapies in SCI/D is primarily based on osteopenia or osteoporosis at the hip by screening DXAs. Gastrointestinal side effects are the major reason for discontinuation of oral bisphosphonates. New therapies for osteoporosis in SCI/D are needed.

Factors influencing providers' decisions on management of bone health in people with spinal cord injury.

STUDY DESIGN: Survey. OBJECTIVES: Managing osteoporosis in persons with chronic spinal cord injury (SCI) is difficult as little evidence exists regarding effective strategies. We examined the effect of key factors on providers' bone health management decisions in persons with SCI. SETTING: USA. METHODS: Providers reviewed blocks of 9 hypothetical cases that varied on four factors: osteoporosis, osteopenia, or normal bone mineral density using dual-energy X-ray absorptiometry (DXA); DXA region of interest (lumbar spine, hip, knee), prior lower extremity fracture; and no or limited ambulation. They indicated how likely they would recommend pharmacological management, what treatment(s) they would recommend, and whether they would request another DXA before treatment. RESULTS: Eighty-two healthcare providers completed the survey. Treatment recommendations for bisphosphonates and Vitamin D/calcium supplements, respectively, were more likely if there was a prior fracture (OR: 2.65, 95%CI: 1.76-3.99, p < 0.0001; OR: 2.96, 95%CI: 1.40-6.26, p = 0.004) and if a DXA scan found osteopenia (OR: 2.23, 95%CI: 1.41-3.54, p = 0.001; OR: 6.56, 95%CI: 2.71-15.85, p < 0.0001) or osteoporosis (OR: 12.08, 95%CI: 7.09-20.57, p < 0.0001; OR: 4.54, 95%CI: 2.08-9.90, p < 0.0001). Another DXA scan was more likely to be requested if there was a prior fracture (OR: 1.75, 95%CI: 1.10-2.78, p = 0.02) but less likely if the person was nonambulatory (OR: 0.41, 95%: 0.19-0.90, p = 0.03). CONCLUSIONS: Prior fracture and DXA findings influenced treatment recommendations for bone health management in SCI. Reliance on lumbar spine scans to determine bone loss and treatment identifies a knowledge gap for which future education is required.

Association of Bisphosphonate Therapy With Incident of Lower Extremity Fractures in Persons With Spinal Cord Injuries or Disorders.

OBJECTIVE: To investigate the association between prescriptions for bisphosphonates; calcium and vitamin D supplements; and receipt of dual-energy x-ray absorptiometry (DXA) screening, and incident fracture risk in men and women with a spinal cord injury (SCI) or disorder (SCID). DESIGN: Propensity-matched case-control analyses. SETTING: United States Veterans Affairs (VA) facilities. PARTICIPANTS: A total of 7989 men and 849 women with an SCID included in VA administrative databases between October 1, 2005 and October 1, 2015 were identified (N=8838). Cases included 267 men and 59 women with a bisphosphonate prescription propensity matched with up to 4 controls. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Incident lower extremity fractures. RESULTS: There was no significant association between prescriptions for bisphosphonates and incident lower extremity fractures in men (odds ratio [OR], 1.04; 95% confidence interval [CI], 0.62-1.77) or women (OR, 1.02; 95% CI, 0.28-3.75). In men, similar null associations were seen among those who were adherent to bisphosphonate therapy (OR, 1.25; 95% CI, 0.73-2.16), were concomitant users of vitamin D and calcium and a bisphosphonate (OR, 1.05; 95% CI, 0.57-1.96), had more than 1 fracture on different dates during the study period (OR, 0.13; 95% CI, 0.02-1.16) and in those who had undergone DXA testing prior to the date of the bisphosphonate prescription and incident fracture (OR, 1.26; 95% CI, 0.69-2.32). CONCLUSIONS: In men with a traumatic SCI and women with a traumatic SCID, bisphosphonate therapies for osteoporosis do not appear to significantly affect fracture risk. Adequately powered randomized controlled trials are needed to definitively demonstrate efficacy of bisphosphonates for fracture prevention in this population. There is a compelling need to identify new medications to prevent fractures in this high-risk population.

Bone Mineral Density Testing in Spinal Cord Injury: 2019 ISCD Official Position.

Spinal cord injury (SCI) causes rapid osteoporosis that is most severe below the level of injury. More than half of those with motor complete SCI will experience an osteoporotic fracture at some point following their injury, with most fractures occurring at the distal femur and proximal tibia. These fractures have devastating consequences, including delayed union or nonunion, cellulitis, skin breakdown, lower extremity amputation, and premature death. Maintaining skeletal integrity and preventing fractures is imperative following SCI to fully benefit from future advances in paralysis cure research and robotic-exoskeletons, brain computer interfaces and other evolving technologies. Clinical care has been previously limited by the lack of consensus derived guidelines or standards regarding dual-energy X-ray absorptiometry-based diagnosis of osteoporosis, fracture risk prediction, or monitoring response to therapies. The International Society of Clinical Densitometry convened a task force to establish Official Positions for bone density assessment by dual-energy X-ray absorptiometry in individuals with SCI of traumatic or nontraumatic etiology. This task force conducted a series of systematic reviews to guide the development of evidence-based position statements that were reviewed by an expert panel at the 2019 Position Development Conference in Kuala Lumpur, Malaysia. The resulting the International Society of Clinical Densitometry Official Positions are intended to inform clinical care and guide the diagnosis of osteoporosis as well as fracture risk management of osteoporosis following SCI.

Predicting osteoporosis medication receipt in Veterans with a spinal cord injury: A retrospective cohort study.

Objective: To describe frequency and predictors of use of pharmacological therapies for osteoporosis in persons with a spinal cord injury (SCI).Design: Retrospective cohort study.Setting: United States Veterans Health Administration (VA) national databases.Participants: 11,048 persons with a traumatic SCI who received VA health care between Fiscal Years (FY) 2005-2015. Pharmacy data from VA's Corporate Data Warehouse were used to identify prescriptions for Food and Drug Administration-approved pharmacological treatments for osteoporosis including bisphosphonates, calcitonin, denosumab, raloxifene and teriparatide.Outcome Measures: Demographics, clinical and SCI-related characteristics, receipt of a dual energy x-ray absorptiometry (DXA), and prevalent lower extremity fractures were examined to determine factors related to receiving a pharmacological agent for osteoporosis.Results: 1,041 persons (9.4%) had a prescription for a pharmacological agent for osteoporosis; the majority (n = 964, 93.0%) were bisphosphonates. There was a significant decline in the number of these prescriptions from FY 2005 (13.0%) to FY 2015 (2.2%). In multivariable analysis, age (>50 years) (OR = 1.60, 95% CI 1.31-1.94); female sex (OR = 4.09, 95% CI 2.74-6.09); opioid (OR = 1.24, 95% CI 1.01-1.51) or corticosteroid (OR = 1.92, 95% CI 1.01-1.51) prescriptions; complete injury (OR = 1.26, 95% CI 1.04-1.53); receipt of a DXA scan (OR = 84.03, 95% CI 59.80-118.07) and prevalent fracture (OR = 5.43, 95% CI 4.13-7.15) were positive predictors. Black race (OR = 0.43, 95% CI 0.33-0.57) and obese BMI (OR = 0.59, 95% CI 0.45-0.76) were negative predictors.Conclusions: Prescriptions for osteoporosis medications for persons with a SCI declined in recent years. The strongest predictors for having filled these prescriptions were having had a DXA or a prevalent fracture.

Estrogen alone and joint symptoms in the Women's Health Initiative randomized trial.

OBJECTIVE: Although joint symptoms are commonly reported after menopause, observational studies examining exogenous estrogen's influence on joint symptoms provide mixed results. Against this background, estrogen-alone effects on joint symptoms were examined in post hoc analyses in the Women's Health Initiative randomized, placebo-controlled, clinical trial. METHODS: A total of 10,739 postmenopausal women who have had a hysterectomy were randomized to receive daily oral conjugated equine estrogens (0.625 mg/d) or a matching placebo. The frequency and severity of joint pain and joint swelling were assessed by questionnaire in all participants at entry and on year 1, and in a 9.9% random subsample (n = 1,062) after years 3 and 6. Logistic regression models were used to compare the frequency and severity of symptoms by randomization group. Sensitivity analyses evaluated adherence influence on symptoms. RESULTS: At baseline, joint pain and joint swelling were closely comparable in the randomization groups (about 77% with joint pain and 40% with joint swelling). After 1 year, joint pain frequency was significantly lower in the estrogen-alone group compared with the placebo group (76.3% vs 79.2%, P = 0.001), as was joint pain severity, and the difference in pain between randomization groups persisted through year 3. However, joint swelling frequency was higher in the estrogen-alone group (42.1% vs 39.7%, P = 0.02). Adherence-adjusted analyses strengthen estrogen's association with reduced joint pain but attenuate estrogen's association with increased joint swelling. CONCLUSIONS: The current findings suggest that estrogen-alone use in postmenopausal women results in a modest but sustained reduction in the frequency of joint pain.

Bone turnover in long-term survivors of childhood acute lymphoblastic leukemia.

BACKGROUND: We investigated the effects of demographic, lifestyle (self-reported smoking status and physical activity levels), cancer-related treatment factors (radiation and chemotherapy), and diet (calcium and vitamin D intake) on bone turnover and the relationship of bone turnover to lumbar spine bone mineral density (BMD) Z-scores (LS-BMD Z-scores) determined by quantitative computed tomography (QCT) in 418 ≥5-year survivors of childhood acute lymphoblastic leukemia (ALL). PROCEDURE: Bone turnover was assessed by biomarkers including serum bone-specific alkaline phosphatase (BALP), osteocalcin (OC), and urinary N-telopeptide of type I collagen indexed to creatinine (NTX/Cr). The 215 males ranged in age from 9 to 36 years (median age 17 years). RESULTS: Age and tanner score were inversely associated with all biomarkers (BALP, OC, NTX/Cr) (P < 0.001). Males had higher BALP and OC than females (P < 0.001). Body mass index (BMI) was inversely associated with OC and NTX/Cr (P < 0.001). There was no significant association of biomarkers with lifestyle related factors, ALL treatment-related factors, dietary calcium, vitamin D, or LS-BMD Z-score. CONCLUSIONS: In this population of long-term survivors of ALL, bone turnover was significantly associated with age, gender, tanner stage, and BMI. ALL-related treatments did not influence bone turnover and bone turnover was not predictive of volumetric LS-BMD Z-score.

Characterisation of the immune response to type I collagen in scleroderma.

This study was conducted to examine the frequency, phenotype, and functional profile of T lymphocytes that proliferate in response to type I collagen (CI) in patients with scleroderma (SSc). Peripheral blood mononuclear cells (PBMCs) from SSc patients, healthy controls, and rheumatoid arthritis disease controls were labeled with carboxy-fluorescein diacetate, succinimidyl ester (CFSE), cultured with or without antigen (bovine CI) for 14 days, and analysed by flow cytometry. Surface markers of proliferating cells were identified by multi-color flow cytometry. T-cell lines were derived after sorting for proliferating T cells (CFSElow). Cytokine expression in CI-responsive T cells was detected by intracellular staining/flow cytometry and by multiplex cytokine bead assay (Bio-Plex). A T-cell proliferative response to CI was detected in 8 of 25 (32%) SSc patients, but was infrequent in healthy or disease controls (3.6%; p = 0.009). The proliferating T cells expressed a CD4+, activated (CD25+), memory (CD45RO+) phenotype. Proliferation to CI did not correlate with disease duration or extent of skin involvement. T-cell lines were generated using in vitro CI stimulation to study the functional profile of these cells. Following activation of CI-reactive T cells, we detected intracellular interferon (IFN)-gamma but not interleukin (IL)-4 by flow cytometry. Supernatants from the T-cell lines generated in vitro contained IL-2, IFN-gamma, GM-CSF (granulocyte macrophage-colony-stimulating factor), and tumour necrosis factor-alpha, but little or no IL-4 and IL-10, suggesting that CI-responsive T cells express a predominantly Th1 cytokine pattern. In conclusion, circulating memory CD4 T cells that proliferate to CI are present in a subset of patients with SSc, but are infrequent in healthy or disease controls.

QCT versus DXA in 320 survivors of childhood cancer: association of BMD with fracture history.

PURPOSE: To assess agreement on diagnosis of diminished bone mineral density (BMD) and correlation between BMD values obtained by dual-energy X-ray absorptiometry (DXA) and quantitative computed tomography (QCT) in childhood cancer survivors. PATIENTS AND METHODS: We retrospectively reviewed lumbar spine QCT and DXA studies for BMD in patients who underwent both imaging studies within a 24-hr period. We determined correlation between BMD values and agreement on diagnosis of diminished BMD obtained by both modalities. Diminished BMD was defined as two or more SDs below mean for age- and gender-matched reference values. We evaluated the relationship of BMD values determined by each modality to self-reported fracture history in the 160 (50%) patients with available reports. RESULTS: Of 320 patients, 56% (178) were male; 87% (277) were white. Median age was 16.4 (range, 5.1-36.0) years. Median BMD Z-score was -1.43 (range, -5.96 to 3.20) by QCT and -1.30 (range, -5.50 to 2.80) by DXA. Correlation between QCT- and DXA-determined BMD values was significant but low, and agreement on diminished BMD was fair (kappa = 0.32). There was no association between BMD measured by either QCT or DXA and self-reported traumatic fracture history. Male gender was associated with doubling the traumatic fracture risk (P = 0.0499). CONCLUSIONS: Quantitative computed tomography and DXA may give discrepant results when used to assess bone health in childhood cancer survivors, especially in those of non-white race. This inconsistency in indicators of BMD deficiency may complicate clinical decision-making. Consecutive use of a single modality is recommended to provide reliable longitudinal information.

Effects of a low sodium diet on bone metabolism.

Osteoporosis is a serious public health problem, and dietary interventions may potentially be helpful in preventing this disorder. The purpose of this study was to determine the effects of a low sodium diet on bone metabolism in postmenopausal women. This was a longitudinal study to determine the effects of a low sodium (2-g/day) diet on bone. Forty postmenopausal African-American and Caucasian women were enrolled in a 2-g/day sodium diet for 6 months. Sodium and calcium excretion, bone turnover, and calcitropic hormones (intact parathyroid hormone (PTH) and 1,25 dihydroxyvitamin D) were measured before and 6 months after the intervention. In women who had baseline sodium excretions equal to or greater than the average sodium intake in the United States (> or =3.4 g/day), the low sodium diet resulted in significant decreases in sodium excretion (P = 0.01), in calcium excretion (P = 0.01), and in a biomarker of bone turnover, aminoterminal propeptide of type I collagen (P = 0.04). However, there were no significant changes in calcitropic hormones, including intact PTH (P = 0.97) or 1,25 dihydroxyvitamin D (P = 0.49) with the low sodium diet. These findings suggest that in postmenopausal women with sodium intakes > or =3.4 g/day, a low sodium diet may have benefits for skeletal health.

The relationship of antiresorptive drug use to structural findings and symptoms of knee osteoarthritis.

OBJECTIVE: To examine the cross-sectional association between use of medications that have a bone antiresorptive effect (estrogen, raloxifene, and alendronate) and both the structural features of knee osteoarthritis (OA), assessed by magnetic resonance imaging (MRI) and radiography, and the symptoms of knee OA in elderly women. METHODS: Women in the Health, Aging and Body Composition Study underwent MRI and radiography of the knee if they reported symptoms of knee OA, and women without significant knee symptoms were selected as controls. MR images of the knee were assessed for multiple features of OA using the Whole-Organ MRI scoring method, and radiographs were read for Kellgren and Lawrence grade and individual features of OA. Concurrent medication use and knee symptoms were assessed by interview, and knee pain severity was evaluated using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). RESULTS: There were 818 postmenopausal women from whom we obtained MR images of the knee and data on medication use. Among these women, 214 (26.2%) were receiving antiresorptive drugs. We found no significant association between overall use of antiresorptive drugs and the presence of knee pain and radiographic changes of OA of the knee. Use of alendronate, but not estrogen, was associated with less severity of knee pain as assessed by WOMAC scores. Both alendronate use and estrogen use were associated with significantly less subchondral bone attrition and bone marrow edema-like abnormalities in the knee as assessed by MRI, as compared with women who had not received these medications. CONCLUSION: Elderly women being treated with alendronate and estrogen had a significantly decreased prevalence of knee OA-related subchondral bone lesions compared with those reporting no use of these medications. Alendronate use was also associated with a reduction in knee pain according to the WOMAC scores.

Association between bone mineral density and the use of nonsteroidal anti-inflammatory drugs and aspirin: impact of cyclooxygenase selectivity.

UNLABELLED: BMD was examined in users of NSAIDs (by COX selectivity) and aspirin in the Health ABC cohort (n = 2853). Significantly higher BMD was found in users of relative COX-2 selective NSAIDs with aspirin (COX-2/ASA) compared with nonusers. This suggests a role for COX-2/ASA in osteoporosis. INTRODUCTION: The purpose of this study was to determine the relationship of nonsteroidal anti-inflammatory drug (NSAID) use, by cyclo-oxygenase selectivity (COX), and aspirin use on bone mineral density (BMD) in participants from the Health, Aging, and Body Composition (Health ABC) population-based cohort. It is known that NSAIDs inhibit the COX enzyme and decrease production of prostaglandins, which are involved in regulation of bone turnover. COX has two isoforms, COX-1 and COX-2. Production of prostaglandins associated with bone loss is primarily mediated through the COX-2 pathway. In addition, aspirin may have effects on bone independent of the prostaglandin pathway. MATERIALS AND METHODS: NSAID (by COX selectivity) and aspirin use and BMD were assessed in 2853 adults (49.5% women, 50.5% men: 43.1% black, 56.9% white; mean age: 73.6 years) from the Health ABC cohort. For the purposes of this analysis, relative COX-1 selective NSAIDs were defined as having a ratio of COX-1 IC50 to COX-2 IC50 of > 1 in whole blood, and relative COX-2 selective NSAIDs were defined as having a ratio of COX-1 IC50 to COX-2 IC50 of < 1 in whole blood. Analysis of covariance was used to compare BMD across each NSAID use and aspirin use category adjusting for age, race, gender, weight, height, study site, calcium and vitamin D supplementation, Womac score, history of rheumatoid arthritis, history of arthritis other than rheumatoid, and smoking status. RESULTS: After adjustment for possible confounders, current use of relative COX-2 selective NSAIDs with aspirin was associated with higher BMD at the whole body (4.2%, 1.2-7.3 CI) and total hip (4.6%, 0.5-8.8 CI) by DXA and at both trabecular (34.1%, 15.4-52.7 CI) and cortical spine (12.8%, 2.3-23.3 CI) by quantitative computed tomography. CONCLUSIONS: Our data suggest that the combination of relative COX-2 selective NSAIDs and aspirin is associated with higher BMD at multiple skeletal sites in men and women.