Rheumatoid arthritis (RA), the most common autoimmune disease, is associated in families with other autoimmune diseases, including insulin-dependent diabetes mellitus (IDDM). Its genetic component has been suggested by familial aggregation (s ‫؍‬ 5), twin studies, and segregation analysis. HLA, which is the only susceptibility locus known, has been estimated to account for one-third of this component. The aim of this paper was to identify new RA loci. A genome scan was performed with 114 European Caucasian RA sib pairs from 97 nuclear families. Linkage was significant only for HLA (P < 2.5⅐10 ؊5 ) and nominal for 19 markers in 14 other regions (P < 0.05). Four of the loci implicated in IDDM potentially overlap with these regions: the putative IDDM6, IDDM9, IDDM13, and DXS998 loci. The first two of these candidate regions, defined in the RA genome scan by the markers D18S68-D18S61-D18S469 (18q22-23) and D3S1267 (3q13), respectively, were studied in 194 additional RA sib pairs from 164 nuclear families. Support for linkage to chromosome 3 only was extended significantly (P ‫؍‬ 0.002). The analysis of all 261 families provided a linkage evidence of P ‫؍‬ 0.001 and suggested an interaction between this putative RA locus and HLA. This locus could account for 16% of the genetic component of RA. Candidate genes include those coding for CD80 and CD86, molecules involved in antigenspecific T cell recognition. In conclusion, this first genome scan in RA Caucasian families revealed 14 candidate regions, one of which was supported further by the study of a second set of families.

Spinal tuberculosis (TB) accounts for about 2% of all cases of TB. New methods of diagnosis such as magnetic resonance imaging (MRI) or percutaneous needle biopsy have emerged. Two distinct patterns of spinal TB can be identified, the classic form, called spondylodiscitis (SPD) in this article, and an increasingly common atypical form characterized by spondylitis without disk involvement (SPwD). We conducted a retrospective study of patients with spinal TB managed in the area of Paris, France, between 1980 and 1994 with the goal of defining the characteristics of spinal TB and comparing SPD to SPwD. The 103 consecutive patients included in our study had TB confirmed by bacteriologic and/or histologic studies of specimens from spinal or paraspinal lesions (93 patients) or from extraspinal skeletal lesions (10 patients). Sixty-eight percent of patients were foreign-born subjects from developing countries. None of our patients was HIV-positive. SPD accounted for 48% of cases and SPwD for 52%. Patients with SPwD were younger and more likely to be foreign-born and to have multiple skeletal TB lesions. Neurologic manifestations were observed in 50% of patients, with no differences between the SPD and SPwD groups. Of the 44 patients investigated by MRI, 6 had normal plain radiographs; MRI was consistently positive and demonstrated epidural involvement in 77% of cases. Bacteriologic and histologic yields were similar for surgical biopsy (n = 16) and for percutaneous needle aspiration and/or biopsy (n = 77). Cultures for Mycobacterium tuberculosis were positive in 83% of patients, and no strains were resistant to rifampin. Median duration of antituberculous chemotherapy was 14 months. Surgical treatment was performed in 24% of patients. There were 2 TB-related deaths. Our data suggest that SPwD may now be the most common pattern of spinal TB in foreign-born subjects in industrialized countries. The reasons for this remain to be elucidated.

Spinal radiologic lesions suggestive of destructive spondylarthropathy were found in 10 patients on longterm hemodialysis. These lesions were characterized by severe narrowing of the intervertebral disc, associated with erosions and geodes of the adjacent vertebral plates without osteophytosis. In 9 of the 10 patients the lesions were located in the cervical spine, and in 1 patient, in the lumbar spine. Microbial spondylitis, degenerative disc disease, and destructive spondylarthropathy of calcium pyrophosphate dihydrate deposition disease were each, in turn, ruled out. The finding of apatite crystals by transmission electron microscopy in 1 disc specimen suggests that these crystals may be associated with destructive vertebral disc lesions in dialysis patients.Hemodialysis can considerably prolong the life span of patients suffering from terminal renal failure. However, it can lead t o various bone and joint complications. In addition to renal osteodystrophy, these complications include infections and acute arthritis or

Synovial amyloid deposits were found in 18 patients with end‐stage renal failure due to various non‐amyloid nephropathies, who had been treated with long‐term, periodic hemodialysis (mean 116 months). All patients had carpal tunnel syndrome, which was bilateral in 14 of them; 4 patients also had finger flexor tenosynovitis. In 2 patients, destructive arthropathies required surgical replacement of the hip. Amyloid deposits were demonstrated by light microscopy in the synovium of the finger flexor tendon and/or transverse carpal ligament of all patients who had surgery for carpal tunnel syndrome, and in the synovium and capsula of the 2 surgically removed hips. Transmission electron microscopy of synovial samples from 6 patients demonstrated the characteristic fibrillar ultrastructure of amyloid deposits, the biochemical nature of which is still unknown. In addition, 9 patients had cystic radiolucencies of bone, which were interpreted as having resulted from local amyloid deposits, involving carpal bones, humeral heads, femoral heads, acetabula, or tibial plateaus. Our results show that amyloidosis is a frequent histologic finding in dialysis patients receiving surgical management of carpal tunnel syndrome, and that it can also be associated with cystic radiolucencies of bones and with destructive arthropathies.

One hundred and forty-five patients suffering from diseases requiring long-term treatment with high doses of corticosteroids (30 mg/day or greater of prednisolone) were recruited to the study. Patients had to be steroid naive on entry to the study (not more than 15 days of treatment with a corticosteroid within the previous 24 months). Patients were randomized to receive either 1 microgram/day alfacalcidol or placebo capsules for 12 months. Bone mineral density (BMD) of the lumbar spine was assessed by dual-photon absorptiometry on entry and after 3, 6 and 12 months' treatment. Safety was monitored by the recording of all adverse events reported by patients and the regular screening of blood samples for hematology and serum biochemistry. Of the 145 patients, 74 were randomized to alfacalcidol and 71 to placebo. The treatment groups were well matched at baseline with no significant differences in demographic, clinical or biochemical parameters. The mean equivalent dose of prednisolone at baseline was 46.6 mg/day and 46.3 mg/day for the alfacalcidol and placebo group respectively. From the 145 patients randomized to treatment, 71 (38 who received alfacalcidol and 33 who received placebo) provided BMD data both at baseline and at 3, 6 and 12 months. The percentage change in BMD after 6 months' treatment was -2.11% in the alfacalcidol group and -4.00% in the placebo group (p = 0.39). After 12 months the percentage change in BMD was +0.39% (CI: -4.28 to 4.81) in the alfacalcidol group and -5.67% (CI: -8.13 to -3.21) in the placebo group, this difference (6.06%, CI: 0.88 to 11.24) being statistically significant (p = 0.02). An intention to treat analysis also showed a significant difference between the two treatment groups in alfacalcidol's favor (3.81%, p = 0.01; CI: 0.92 to 6.70). There was no significant difference between the two treatment groups in the corticosteroid dose at any time point during the study. Serum calcium was measured throughout and there were no significant differences between the two treatment groups at any visit. This study suggests that alfacalcidol can prevent corticosteroid-induced bone loss from the lumbar spine. Long-term use of alfacalcidol was not associated with any significant adverse effects in this diverse group of patients.

Severe idiopathic osteoporosis in middle-aged men is still poorly understood. The aim of this study was to assess the contribution of genetic factors in these patients. We studied 38 men (mean age ؎ SD, 50 ؎ 11 years) presenting with vertebral or peripheral bone fractures due to primary osteoporosis and 73 of their relatives divided into four subgroups: 19 brothers, 22 sisters, 13 sons, and 19 daughters. The control group comprised 199 age-matched subjects. In all subjects, we measured bone mineral density (BMD) and calculated the Z score at the lumbar spine (LS) and femoral neck (FN) based on the fitted BMD value in the controls. LS BMD values were lower in each of the four subgroups compared with the age-matched controls. The mean Z score for the overall group of 73 relatives was decreased compared with the age-matched controls (-1.28 ؎ 1.48 at the LS and -1.03 ؎ 1.19 at the FN) and was not influenced by gender or by whether the relatives were siblings or children. An LS Z score < -1) was found in 54.8% of the relatives of osteoporotic patients versus 17.4% of the control subjects (risk ratio, 3.2). Alcohol and tobacco abuse are well-known risk factors for osteoporosis in men. Among the 38 osteoporotic patients, 7 were heavy smokers (>20 pack-years), 8 were both heavy smokers and drinkers (>80 g/day for at least 10 years and ␥GT > 40 UI/l), and 23 had neither of these risk factors. BMD, Z score, and anthropometric data were the same in patients with and without risk factors. Decreases in LS and FN Z scores were similar in relatives of patients with and without risk factors. In conclusion, low BMD is observed in relatives of osteoporotic men with or without risk factors for osteoporosis, indicating that familial factors contribute to primary osteoporosis in middle-aged men. (J Bone Miner Res 1998;13: [1909][1910][1911][1912][1913][1914]

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