Association of HLA-DRB1 amino acid residues with giant cell arteritis: genetic association study, meta-analysis and geo-epidemiological investigation.

Introduction: Giant cell arteritis (GCA) is an autoimmune disease commonest in Northern Europe and Scandinavia. Previous studies report various associations with HLA-DRB1*04 and HLA-DRB1*01; HLA-DRB1 alleles show a gradient in population prevalence within Europe. Our aims were (1) to determine which amino acid residues within HLA-DRB1 best explained HLA-DRB1 allele susceptibility and protective effects in GCA, seen in UK data combined in meta-analysis with previously published data, and (2) to determine whether the incidence of GCA in different countries is associated with the population prevalence of the HLA-DRB1 alleles that we identified in our meta-analysis.

Mapping trabecular disconnection "hotspots" in aged human spine and hip.

Trabecular bone disconnection is an independent factor in age-related skeletal failure where real termini (ReTm; rare in youth) may cause weakness disproportionate to tissue loss, yet their structural contribution at vulnerable locations remains uncertain. ReTm (previously recorded at the iliac crest) were mapped in "normal" aged vertebral bodies (T11-L5 autopsy; 20 females, 10 males) and corresponding proximal femora (autopsy; 10 females). Results were compared with biomechanically failed femora from orthopaedic subjects aged >58 yr (osteoporosis OP, 10 females; osteoarthritis OA, 10 females).

A large-scale genetic analysis reveals a strong contribution of the HLA class II region to giant cell arteritis susceptibility.

We conducted a large-scale genetic analysis on giant cell arteritis (GCA), a polygenic immune-mediated vasculitis. A case-control cohort, comprising 1,651 case subjects with GCA and 15,306 unrelated control subjects from six different countries of European ancestry, was genotyped by the Immunochip array. We also imputed HLA data with a previously validated imputation method to perform a more comprehensive analysis of this genomic region.

Ischaemic manifestations in giant cell arteritis are associated with area level socio-economic deprivation, but not cardiovascular risk factors.

Objectives: To determine whether ischaemic manifestations of GCA are associated with pre-existing hypertension, atherosclerosis or area-level socio-economic deprivation.

Methods: We conducted an observational study of rheumatologist/ophthalmologist-diagnosed GCA in eight UK centres. The main outcome measure was ischaemic manifestations observed during active GCA: visual loss/blurring, aura, diplopia, jaw/tongue/limb claudication, cerebral/myocardial ischaemia or scalp necrosis.

An unusual case of testicular pain.

We present the first case of lupus presenting with testicular pain in an Asian man. This gentleman presented with clear features of lupus with fever, joint pain, rash, diarrhoea and vomiting. He had typical serology consistent with active lupus.

Effect of the early use of the anti-tumor necrosis factor adalimumab on the prevention of job loss in patients with early rheumatoid arthritis.

Objective: To compare work disability and job loss in early rheumatoid arthritis (RA) patients receiving adalimumab plus methotrexate (adalimumab + MTX) versus MTX alone.

Methods: In this multicenter, randomized, controlled trial, patients with RA for <2 years who had never taken MTX and who self-reported work impairment were randomized to adalimumab + MTX or placebo + MTX for 56 weeks. Primary outcome was job loss of any cause and/or imminent job loss at or after week 16.

Preservation of thoracic spine microarchitecture by alendronate: comparison of histology and microCT.

The effect of bisphosphonates on trabecular microarchitecture may contribute to the reduced risk of vertebral fracture with treatment independent of the bone volume. Trabecular structure was examined at the twelfth thoracic vertebra after 2 years of treatment of two groups of ovariectomized baboons on high and low doses of alendronate, compared with ovariectomized and non-ovariectomized controls. Standard 2D histological measurements showed that alendronate treatment of ovariectomized animals resulted in significantly higher total trabecular length and a lower marrow star volume in comparison with ovariectomized controls indicating preservation of connectivity.

Predictors of outcome in patients with oligoarthritis: results of a protocol of intraarticular corticosteroids to all clinically active joints.

Objective: To determine the outcome and the factors that predict the persistence of synovitis following intraarticular corticosteroid injections in patients with recent-onset oligoarthritis.

Methods: Fifty-one patients with < or =5 joints with synovitis (disease duration < or =12 months) were treated with intraarticular injections of methylprednisolone into all joints with clinical synovitis. Predictors of outcome were sought, with the primary end point a complete response (no synovitis on clinical examination) at 12 weeks.

Trabecular architecture in women and men of similar bone mass with and without vertebral fracture: I. Two-dimensional histology.

While osteoporosis is characterized by a low bone mass there is a well-recognized overlap in bone mineral density (BMD) measurements between groups of subjects with and without vertebral fracture. To investigate whether differences in trabecular architecture may contribute to the presence or absence of fractures independent of the bone mass, fracture and nonfracture groups matched for age, gender, and BMD were assembled. Transiliac biopsies and corresponding lumbar spine BMD measurements from 31 women and 16 men with vertebral fracture were compared with those from 22 women and 11 men without fracture.

Assessment of renal osteodystrophy in dialysis patients: use of bone alkaline phosphatase, bone mineral density and parathyroid ultrasound in comparison with bone histology.

Bone biopsies were studied in 73 patients to determine if a two-site radioimmunometric assay for serum bone alkaline phosphatase (BAP), total serum alkaline phosphatase (ALP), serum intact parathyroid hormone (iPTH), hand X-rays, regional bone mineral density (BMD) measurements and parathyroid enlargement detected by ultrasonography could accurately predict renal osteodystrophy. In the patients studied 57 had hyperparathyroid bone disease, 4 mixed renal osteodystrophy, 3 adynamic bone disease, 1 osteomalacia and 8 normal histology. Serum BAP, ALP and iPTH correlated positively with mineral apposition rate, osteoblastic, osteoid and eroded surface.

Endocrine disorders.

The effect of endocrine disorders on bone mass is being increasingly studied. It is suggested that the preceding thyroid disorder, rather than thyroxine replacement itself, may reduce bone mass. Fracture rate does not appear to be increased in primary hyperparathyroidism once the condition is diagnosed.

Primary generalized osteoarthritis and bone mass.

The association of OA with increased bone mass is controversial. This study measured BMD at the hip and spine and total body bone mineral (TBBM) by dual energy X-ray absorptiometry, and BMD at the distal forearm by single photon absorptiometry in 20 post-menopausal women with primary generalized OA. The data were compared with those from 89 normal controls.

Endocrine disease.

The effects of endocrine disease on bone mass continue to attract attention. Investigations include the effects on the skeleton of thyroid disease, primary hyperparathyroidism, and their treatment. The effect of growth hormone replacement in adults with panhypopituitarism has also been investigated; children with treated growth hormone deficiency appear to reach adulthood with low bone mass.

Urinary excretion of pyridinium crosslinks of collagen in patients with osteoporosis and the effects of bone fracture.

Values for the urinary excretion of pyridinium crosslinks of collagen, pyridinoline and deoxypyridinoline, in a group of 30 elderly women with femoral fractures associated with osteoporosis and a group of 20 women without recent fracture but with overt or suspected osteoporosis were compared with 27 control subjects matched for age. Relative to the control group, the excretion of the crosslinks was significantly higher in the group with fractures and the group with osteoporosis. Fractures contributed markedly to the excretion of pyridinium crosslinks as the patients with fractures showed significantly higher excretion of pyridinoline and deoxypyridinoline than the group without recent fractures.

Endocrine disorders.

The effect of thyroxine replacement therapy on bone mass continues to attract attention. Although the advice of the American Thyroid Association to normalize serum thyroxine and thyroid-stimulating hormone concentrations is recommended, even physiologic doses of thyroxine may have an adverse effect on bone mass. The diagnosis and treatment of osteomyelitis in the diabetic foot is aided by magnetic resonance imaging, and long-term review of cases of diabetic femoral neuropathy emphasizes the good prognosis.

Renal tubular dysfunction in rheumatic diseases.

Evidence of renal tubular dysfunction as defined by abnormal urinary levels of alpha 1 and beta 2 microglobulin with or without microalbuminuria was found in 47 (16.5%) of 285 patients with a variety of rheumatic diseases, compared with a prevalence of less than 1% in 500 healthy adults. Previous work from this unit has shown a prevalence of tubular dysfunction of 24% in patients with severe rheumatic disease admitted to hospital, probably associated with severe rheumatoid arthritis.

Endocrine disorders.

Recent studies emphasize the adverse effects of endocrine disorders on bone mass. Successful surgery for hyperparathyroidism results in an increase in bone mass, although impact on future fracture rates in these patients is unknown. The etiology of reduced bone mass in diabetes is still unclear, and the adverse effects of thyroxine replacement treatment on bone mass need to be carefully balanced against beneficial effects on hypercholesterolemia.

The architecture of cancellous and cortical bone in femoral neck fracture.

The architecture of cancellous bone as well as quantity and quality is considered important in maintaining mechanical integrity. To determine whether abnormalities of architecture occur in femoral neck fracture we measured trabecular width and number in iliac crest bone biopsies of 68 women with femoral fracture and compared them with data from a postmortem series of age-matched women without known bone disease. Cortical thickness was measured in 27 of the fracture patients and 17 controls.