Degenerative inter-vertebral disc disease osteochondrosis intervertebralis in Europe: prevalence, geographic variation and radiological correlates in men and women aged 50 and over.

Objectives: To assess the prevalences across Europe of radiological indices of degenerative inter-vertebral disc disease (DDD); and to quantify their associations with, age, sex, physical anthropometry, areal BMD (aBMD) and change in aBMD with time. Methods: In the population-based European Prospective Osteoporosis Study, 27 age-stratified samples of men and women from across the continent aged 50+ years had standardized lateral radiographs of the lumbar and thoracic spine to evaluate the severity of DDD, using the Kellgren-Lawrence (KL) scale. Measurements of anterior, mid-body and posterior vertebral heights on all assessed vertebrae from T4 to L4 were used to generate indices of end-plate curvature. Results: Images from 10 132 participants (56% female, mean age 63.9 years) passed quality checks. Overall, 47% of men and women had DDD grade 3 or more in the lumbar spine and 36% in both thoracic and lumbar spine. Risk ratios for DDD grades 3 and 4, adjusted for age and anthropometric determinants, varied across a three-fold range between centres, yet prevalences were highly correlated in men and women. DDD was associated with flattened, non-ovoid inter-vertebral disc spaces. KL grade 4 and loss of inter-vertebral disc space were associated with higher spine aBMD. Conclusion: KL grades 3 and 4 are often used clinically to categorize radiological DDD. Highly variable European prevalences of radiologically defined DDD grades 3+ along with the large effects of age may have growing and geographically unequal health and economic impacts as the population ages. These data encourage further studies of potential genetic and environmental causes.

Clinical efficacy of oral alendronate in ankylosing spondylitis: a randomised placebo-controlled trial.

OBJECTIVES: A prospective, double blind, randomised, placebo controlled trial over 2 years was performed to test the efficacy of alendronate, an oral aminobisphosphonate, in improving symptoms and arrest disease progression in patients with mild to severe ankylosing spondylitis (AS). METHODS: 180 patients with AS were randomised to receive weekly alendronate 70 mg or placebo (1:1 randomisation). BAS-G was the primary outcome measure with Bath indices as secondary outcomes. Vertebral x-rays were performed at 0 and 24 months. Biomarkers (including CRP, IL-1beta, IL6, VEGF, MMP-1, and MMP-3) were collected during the first 12 months. RESULTS: There was no significant difference between the placebo and treatment groups in any of the recorded outcomes over the 2 years including clinical indices, biomarkers, and radiology. The change in BAS-G, the primary outcome measure, was -0.21 for the treatment group and -0.42 for the placebo group p=0.57. Change in all other clinical outcome measures were also non-significant; BASDAI p=0.86, BASFI p=0.37, BASMI p=0.021. Sub-group analysis of those subjects with a baseline BASDAI >4 were also non-significant. CONCLUSIONS: This prospective study demonstrates that alendronate 70mg weekly for 2 years was no more efficacious than placebo in improving clinical or laboratory measures of disease activity or measures of physical impact in subjects with mild to severe active AS. TRIAL REGISTRATION: ID SRCTN12308164, registered on 15.12.2015.

Severe polyarthritis secondary to zolendronic acid: a case report and literature review.

Intravenous zolendronic acid is an established anti-resorptive treatment for post-menopausal osteoporosis and is usually well tolerated. Common side effects, including the classical 'acute phase response', are consented for prior to treatment. However, rare but serious adverse reactions to zolendronic acid have been described. We report the case of an older patient with osteoporosis and osteoarthritis who presented within 12 hours of her first zolendronic acid infusion with evidence of a severe acute polyarthritis affecting her peripheral appendicular skeleton, in joints affected by pre-existing osteoarthritis. Despite the prevalence of osteoarthritis, this is the most severe case of polyarthritis following intravenous zolendronic acid to date and only the second reported case. We remind prescribing physicians treating patients with intravenous bisphosphonates, to bear in mind possible rare serious adverse reactions as well as common benign side effects. We postulate age-associated frailty may reduce tolerability to even milder acute phase reactions.

Association of cytokine and matrix metalloproteinase profiles with disease activity and function in ankylosing spondylitis.

INTRODUCTION: The pathology of ankylosing spondylitis (AS) suggests that certain cytokines and matrix metalloproteinases (MMPs) might provide useful markers of disease activity. Serum levels of some cytokines and MMPs have been found to be elevated in active disease, but there is a general lack of information about biomarker profiles in AS and how these are related to disease activity and function. The purpose of this study was to investigate whether clinical measures of disease activity and function in AS are associated with particular profiles of circulating cytokines and MMPs. METHODS: Measurement of 30 cytokines, five MMPs and four tissue inhibitors of metalloproteinases was carried out using Luminex® technology on a well-characterised population of AS patients (n = 157). The relationship between biomarker levels and measures of disease activity (Bath ankylosing spondylitis disease activity index (BASDAI)), function (Bath ankylosing spondylitis functional index) and global health (Bath ankylosing spondylitis global health) was investigated. Principal component analysis was used to reduce the large number of biomarkers to a smaller set of independent components, which were investigated for their association with clinical measures. Further analyses were carried out using hierarchical clustering, multiple regression or multivariate logistic regression. RESULTS: Principal component analysis identified eight clusters consisting of various combinations of cytokines and MMPs. The strongest association with the BASDAI was found with a component consisting of MMP-8, MMP-9, hepatocyte growth factor and CXCL8, and was independent of C-reactive protein levels. This component was also associated with current smoking. Hierarchical clustering revealed two distinct patient clusters that could be separated on the basis of MMP levels. The high MMP cluster was associated with increased C-reactive protein, the BASDAI and the Bath ankylosing spondylitis functional index. CONCLUSIONS: A profile consisting of high levels of MMP-8, MMP-9, hepatocyte growth factor and CXCL8 is associated with increased disease activity in AS. High MMP levels are also associated with smoking and worse function in AS.

Management of osteoporosis in a pre-menopausal woman.

There is no agreed definition of osteoporosis in pre-menopausal women. The International Society for Clinical Densitometry recommends using Z-score, and women with Z-scores of -2.0 or lower should be defined as having a bone density that is 'below the expected range for age'. The diagnosis is more readily made in the presence of a low-trauma fracture. The relationship between low bone mineral density (BMD) in young pre-menopausal women and its associated fracture risk is not the same as in older women with a low BMD. Between 50% and 90% of pre-menopausal women will have an underlying secondary cause, the most common being eating disorders, anorexia nervosa and use of glucocorticoids. Management should focus on identifying the underlying cause and treating it where possible. The use of pharmacological therapy under other circumstances should be considered carefully. Women with only low BMD and no other risk factors probably require no pharmacological intervention. Those with low BMD and secondary causes or with a severely low BMD, or those who have fragility fractures, may require treatment with anti-resorptive agents, which can include oestrogen, bisphosphonates, calcitonin, calcitriol or anabolic therapy with teriparatide. Selective oestrogen receptor modulators (SERMs) should be avoided as they cause further bone loss in menstruating women. Alendronate and risedronate have been licensed for use in glucocorticoid-induced osteoporosis. These drugs accumulate in the human skeleton and have been shown to cross the placenta and accumulate in newborn rats. The effects on human pregnancy are unclear, although normal pregnancies have been reported. Pre-menopausal women with osteoporosis should be followed up until the BMD is stable, which can usually be ascertained by follow-up scans at 18-36-month intervals.

Lateral back pain identifies prevalent vertebral fractures in post-menopausal women: cross-sectional analysis of a primary care-based cohort.

OBJECTIVE: Vertebral fractures (VFs) are frequently under-recognized, reflecting their lack of diagnostic clinical features. For example, although VFs are associated with back pain, this is also common in the general population. To establish whether back pain can be used to recognize patients with VF, we investigated the site of pain in people with and without VFs using a simple tool. METHODS: A cohort of 504 post-menopausal women was recruited from primary care in South West UK. Back pain was assessed by self-completion of the Margolis pain diagram, and analysis was modified to assess whether pain was mid-line or lateral. VFs were diagnosed by the algorithm-based qualitative method on radiographs. A cross-sectional analysis was carried out to assess the association between back pain and VFs. RESULTS: Three hundred and twenty-two women (64.1%) reported back pain over the last 12 months. Thirty seven (7.3%) had one or more VFs. In women with back pain, the presence of lateral waist area pain was associated with a 4.5-fold increased risk of VFs [odds ratio (OR) 4.48; 95% CI 2.02, 9.94; P < 0.001]. CONCLUSIONS: In post-menopausal women with back pain, the presence of lateral waist pain, as shown on the Margolis pain diagram, may identify women at higher risk of prevalent VF.

Bone mineral density, calcaneal ultrasound, and bone turnover markers in women with ankylosing spondylitis.

OBJECTIVE: To assess bone mineral density (BMD) by dual energy x-ray absorptiometry (DEXA) and calcaneal quantitative ultrasound (QUS) in a cohort of pre- and postmenopausal women with ankylosing spondylitis (AS), and to determine any relationships with markers of bone turnover and disease activity or severity. METHODS: Fifty premenopausal and 16 postmenopausal women with AS were studied. Clinical and radiological status was assessed by the Bath AS Disease Activity Index (BASDAI), Bath AS Functional Index (BASFI), Bath AS Metrology Index (BASMI), and Bath AS Radiology Index (BASRI). BMD of the hip and spine was measured by DEXA, and QUS measured at the heel. Serum osteocalcin (OC), bone-specific alkaline phosphatase (BALP), urinary D-pyridinoline crosslinks (D-PYR), and C-reactive protein (CRP) were assayed. RESULTS: Women with AS (n = 66) had reduced BMD at the hip compared to age and sex matched controls (n = 132). The mean t scores were -1.1 and -2.0, and z scores -0.4 and -0.37, for pre- and postmenopausal women, respectively. Four (6%) had osteoporosis and 34 (52%) had osteopenia according to the WHO definitions. Using a multiple regression model, femoral neck BMD was found to be significantly affected by age, body mass index, and the sacroiliac radiographic score. There were no significant correlations of BMD with disease duration or disease activity. QUS measures did not correlate with DEXA measures of BMD. Women with AS had significantly lower markers of bone formation, OC and BALP, and a trend to higher D-PYR than controls. Serum OC levels correlated negatively with femoral neck BMD, whereas D-PYR correlated with CRP levels. CONCLUSION: Women with AS have reduced hip BMD, 0.39 SD below age and sex matched controls. Bone turnover in women with AS is characterized by low OC and BALP.