The occurrence of vertebral fracture was examined cross-sectionally and longitudinally over a 4-year interval in 117 menopausal and postmenopausal Japanese women with rheumatoid arthritis (RA), whose ages ranged from 50 to 64 years. Patients treated with bisphosphonate were excluded. Vertebral fracture was diagnosed by lateral thoracic and lumbar spine radiography at the start and end of a 4-year period. Bone mineral density (BMD) at L2-L4 according to dual-energy X-ray absorptiometry (DXA), the administration of corticosteroids or methotrexate, and urinary excretion of N-telopeptide of type I collagen (NTx) were also recorded. In the cross-sectional study, the prevalence of vertebral fracture in the initial radiographs of RA patients was 21%, while it was 5% in healthy age-matched controls. Among RA patients treated with corticosteroids, 33% had vertebral fracture, which was a significantly higher prevalence than that in RA patients without steroid administration. In the longitudinal study, vertebral fracture prevalence was also increased in patients more than 60 years old. RA patients having steroid treatment and a BMD/YAM (young adult mean) ratio below 70% had higher risk of vertebral fracture than patients with a BMD/YAM ratio of 70%-80%, which in turn exceeded the risk with a BMD of 80% or more. No adverse effect of low-dose methotrexate on vertebral fracture was found. Urinary NTx was high in RA patients, as reported previously, and did not differ between patients with or without new fracture after 4 years. In conclusion, Japanese RA patients more than 60 years old who were treated with corticosteroid or had a BMD below 80% had high risk of vertebral fracture.

The growth plate is a specialized structure that is responsible for longitudinal bone growth (LGR). Growth plate organization is altered with loading in rats. Parathyroid hormone (PTH) is known to induce mitogenic effect on chondrocytes in vitro. Type I PTH/PTH related peptide (rP) receptor is expressed in growth plate cartilage in rats. We therefore investigated the effect of PTH administration on the organization and longitudinal growth rate of the growth plate in rats. We also investigated the effect of PTH on the changes induced by unloading in the organization and growth of the growth plate. Thirty 6-week-old and 30 15-week-old male Sprague-Dawley rats were randomly assigned to five groups (n = 6 per group), i.e., basal controls, control (i.e., normally loaded), PTH-treated control (i.e., PTH-treated under normal loading), unloaded, and PTH-treated under unloading. PTH-treated animals received human PTH (1-34) at a dose of 80 microg/kg per day five times per week for 3 weeks, for the duration of unloading. In young loaded rats treated with the systemic administration of PTH, growth plate thickness, chondrocyte number, and LGR were increased in the proximal tibiae compared with findings in young loaded rats without PTH administration. Hindlimb unloading induced a reduction in growth plate thickness, chondrocyte number, and LGR. In young rats, systemic administration of PTH partly prevented these changes induced by unloading. These preventive effects of PTH were observed only in young rats; not in adult rats. These results show that the systemic administration of PTH stimulates longitudinal bone growth, and diminishes the reduction in growth plate growth induced by unloading in young rats.

No abstract

Hypogammaglobulinemia is a reduction or absence of immunoglobulin, which may be congenital or associated with immunosuppressive therapy. In addition to infectious diseases, autoimmune diseases have also been reported in patients with hypogammaglobulinemia. A 26-year-old man with hypogammaglobulinemia had multiple joint pain and swelling with erosive changes in the proximal interphalangeal joint of the right middle finger on X-ray film, mimicking rheumatoid arthritis (RA). As polyarthritis remained after immunoglobulin replacement therapy and there was no finding indicating any infection at that time, a diagnosis of RA was made. Prednisolone and etanercept were started. However, his polyarthritis did not improve and he developed meningitis and massive brain ischemia. Finally, a diagnosis of disseminated Mycoplasma hominis infection was made. The differential diagnosis of polyarthritis in patients with hypogammaglobulinemia should strictly exclude Mycoplasma infection by culture with special media or longer anaerobic culture, and molecular methods for mycoplasma.

We analyzed the effect of glucocorticoid on bone regeneration after bone marrow ablation in tibiae of 8-week-old rats. Methylprednisolone sodium succinate (MPSS) was injected intramuscularly at a dose of 100 mg/kg/day for 3 days. Tibiae on days 1, 3, 5, 7, 10, 12, and 14 after ablation were subjected to tartrate-resistant acid phosphatase staining, immunohistochemistry, in situ hybridization, and transmission electron microscopy (TEM), and measurement of the volume of newly-formed bone and the osteoclast number. MPSS significantly decreased the newly-formed bone volume on day 7, and immature bone still remained on day 10 in the MPSS-treated group. The volume of this bone was significantly higher than that in the control group. However, there were no differences between the groups in the osteoclast number, the expression of mRNAs for osteoblast differentiation markers, and alkaline phosphatase and cathepsin K judged by immunohistochemistry. TEM findings showed no difference in the form of osteoblasts, whereas osteoclasts in the MPSS-treated group had less developed ruffled borders, compared to those in the control group. These results suggest that MPSS treatment affects neither the differentiation nor the shape of osteoblasts, and does not change the osteoclast number or the cathepsin K level. However, high dose MPSS inhibits both bone formation and resorption during bone regeneration after rat tibial bone marrow ablation, and inhibits ruffled border formation in osteoclasts. These data will be useful to develop bone regenerative therapies for bone diseases due to high dose steroid administration.