Effects of teriparatide in postmenopausal women with osteoporosis pre-treated with bisphosphonates: 36-month results from the European Forsteo Observational Study.

OBJECTIVES: To describe fracture rates, back pain, and health-related quality of life (HRQoL) in postmenopausal women with osteoporosis and prior bisphosphonate therapy, treated with teriparatide for up to 18 months and followed up for a further 18 months. DESIGN: Prospective, multinational, and observational study. METHODS: Data on prior bisphosphonate use, clinical fractures, back pain visual analog scale (VAS), and HRQoL (EQ-5D) were collected over 36 months. Fracture data were summarized in 6-month intervals and analyzed using logistic regression with repeated measures. Changes from baseline in back pain VAS and EQ-VAS were analyzed using a repeated measures model. RESULTS: Of the 1581 enrolled patients with follow-up data, 1161 (73.4%) had a history of prior bisphosphonate use (median duration: 36 months). Of them, 169 (14.6%) sustained ≥1 fracture during 36-month follow-up. Adjusted odds of fracture were significantly decreased at each 6-month interval compared with the first 6 months of teriparatide treatment: 37% decrease in the 12 to <18 months period during teriparatide treatment (P=0.03) and a 76% decrease in the 12- to 18-month period after teriparatide was discontinued (P<0.001). Significant reductions in back pain and improvement in HRQoL were observed. CONCLUSIONS: Postmenopausal women with severe osteoporosis previously treated with bisphosphonates had a significant reduction in the incidence of fractures compared with the first 6 months of therapy, a reduction in back pain and an improvement in HRQoL during up to 18 months of teriparatide treatment. These outcomes were still evident for at least 18 months after teriparatide was discontinued. The results should be interpreted in the context of an uncontrolled, observational study in a routine clinical setting.

Fracture rate and back pain during and after discontinuation of teriparatide: 36-month data from the European Forsteo Observational Study (EFOS).

UNLABELLED: In this observational study in postmenopausal women with severe osteoporosis, the incidence of fractures was decreased during 18 months of teriparatide treatment with no evidence of further change in the subsequent 18-month post-teriparatide period when most patients took other osteoporosis medications. Fracture reduction was accompanied by reductions in back pain. INTRODUCTION: To describe fracture outcomes and back pain in postmenopausal women with severe osteoporosis during 18 months of teriparatide treatment and 18 months post-teriparatide in normal clinical practice. METHODS: The European Forsteo Observational Study (EFOS) was a prospective, multinational, observational study. Data on incident clinical fractures and back pain (100 mm Visual Analogue Scale [VAS] and questionnaire) were collected. Fracture data were summarised in 6-month intervals and analysed using logistic regression with repeated measures. Changes from baseline in back pain VAS were analysed using a repeated measures model. RESULTS: A total of 208 (13.2%) of 1,576 patients sustained 258 fractures during 36 months of follow-up: 34% were clinical vertebral fractures and 66% non-vertebral fractures. The adjusted odds of fracture were reduced during teriparatide treatment and there was no evidence of further change in the 18-month post-teriparatide period, during which 63.3% patients took bisphosphonates. A 74% decrease in the adjusted odds of fracture in the 30- to <36-month period compared with the first 6-month period was observed (p < 0.001). Back pain decreased during teriparatide treatment and this decrease was sustained after teriparatide discontinuation. Adjusted mean back pain VAS decreased by 26.3 mm after 36 months (p < 0.001) from baseline mean of 57.8 mm. CONCLUSIONS: In a real-life clinical setting, the risk of fracture decreased during teriparatide treatment, with no evidence of further change after teriparatide was discontinued. The changes in back pain seen during treatment were maintained for at least 18 months after teriparatide discontinuation. These results should be interpreted in the context of the design of an observational study.

[Shoulder arthritis due to Haemophilus aphrophilus]. / Arthrite d'épaule à Haemophilus aphrophilus.

We report a case of shoulder arthritis due to Haemophilus aphrophilus. The patient, a 56 year-old woman, was immunocompetent. She presented with a septic arthritis of the left shoulder without portal of entry. A synovial fluid sample was cultured and positive for a gram-negative bacillus after 8 days. It was identified as Haemophilus aphrophilus, in the HACCEK group, by PCR ARN 16S. We did not find any associated endocarditis. The patient recovered. As far as we know, this is only the 5th reported case of arthritis due to this microorganism.

Adult-onset idiopathic phosphate diabetes. I. Chronic pseudoinflammatory back pain and osteopenia.

STUDY OBJECTIVE: to investigate clinical, laboratory test, and bone mineral density abnormalities in 19 adults with phosphate diabetes of unknown etiology diagnosed in a rheumatology department on the basis of a maximal rate for tubular reabsorption of phosphate (TmPO4/GFR) of 0.77 or less. RESULTS: there were 14 males and five females with a mean age of 36.7 years (range 20 to 68 years) at symptom onset and 43.9 years (24-70) at diagnosis. Seventeen patients (90%) had back pain and 13 (68%) had nerve root pain. The pain was nocturnal only or both nocturnal and diurnal in 14 cases (74%). Other manifestations were fatigue (n = 7, 37%), myalgia (n = 6, 32%), fracture (n = 6, 32%), renal colic (n = 4, 21%), and pseudodepression (n = 10, 53%). Laboratory test abnormalities were as follows: serum phosphate, 0.72 mmol/L (0.58-0.89); rate for tubular reabsorption of phosphate, 74% (54-84%); maximal rate for tubular reabsorption of phosphate, 0.58 (0.4-0.76); urinary calcium/urinary creatinine > 0.48 in nine patients (47%); and fractional potassium excretion > 20% in seven patients (37%). Normal values were found for serum levels of Ca++, Na++, Mg++, creatinine, cortisol, T3, T4, TSH, 25(OH)D3, and 1,25(OH)2 D3. Tests for glycosuria and amino aciduria were negative. Bone mineral density measurements showed z-scores of -2.13 (+0.9 to -4.25) at L2-L4, and -1.34 (+1.5 to -3.2) at the femoral neck. Bone histology showed osteoporosis with a mild increase in osteoid deposition. CONCLUSIONS: idiopathic adult-onset phosphate diabetes manifests as chronic back pain and nerve root pain, sometimes with fatigue and depression. Bone mineral density values are decreased and histology shows osteopenia. Differential diagnoses include spondyloarthropathy, disk disease, fibromyalgia, and depression. Determination of the maximal rate for tubular reabsorption of phosphate is the only means of establishing the diagnosis.

Evidence for GM-CSF receptor expression in synovial tissue. An analysis by semi-quantitative polymerase chain reaction on rheumatoid arthritis and osteoarthritis synovial biopsies.

Granulocyte macrophage colony stimulating factor (GM-CSF) is one of the main cytokines involved in tissue damage during rheumatoid arthritis (RA). To investigate the expression of the GM-CSF receptor (GM-CSF-R) in the synovial tissue of osteoarthritic (OA) and RA patients, biopsy specimens were obtained ex vivo during therapeutic arthroscopy. A semi-quantitative polymerase chain reaction (PCR) technique was performed using specific primers for the alpha chain of the GM-CSF-R and for beta-actin. The PCR products were analyzed after slot-blotting and hybridization with specific cDNA probes. Both RA (n = 11) and OA (n = 7) samples were positive. No significant overexpression correlating with the clinical or histological disease status of the patients was observed. In conclusion, GM-CSF-R could be detected in the synovial tissue where it can mediate the effects of this cytokine locally produced during RA inflammation.

[Hyperparathyroidism disclosed by forward sagging of the head]. / Une hyperparathyroïdie révélée par une chute de la tête.

An unusual clinical presentation of hyperparathyroidism is reported. The 73-year-old patient was unable to maintain her head upright after ten minutes of walking or standing. Parathyroid adenoma was diagnosed on the basis of ultrasound and pathological findings and parathyroid hormone assays. Following surgery the forward sagging of the head no longer occurred and serum levels of calcium and phosphorus returned to normal. Pathophysiological hypotheses are discussed. No similar cases with isolated weakness of the cervical and dorsal paravertebral muscles has been reported to date.

Major immunoglobulin capping deficiency in the peripheral blood B cells of patients with Sjögren's syndrome.

The capping of surface immunoglobulins (sIg) is a major characteristic of normal B lymphocytes. Thus, we have investigated sIg capping by peripheral blood (PB) B cells of patients with Sjögren's syndrome (SS) and we have found a major deficiency in these patients. In 12 healthy donors (HD), 8 +/- 2.8% of PB mononuclear cells were B cells (i.e. expressing the B-cell antigens CD19, CD20 and CD21 simultaneously) and more than 90% of these PB B cells were able to cap their sIg. In 12 experiments performed using PB lymphocytes from seven patients with SS, a major capping deficiency was noted with only 30% of PB B lymphocytes being able to cap sIg. This defect was not related to an expansion of the B-cell subpopulation expressing the CD5 antigen and was not observed in five patients with rheumatoid arthritis lacking SS. Capping of sIg via antigen binding (i.e. antigenic modulation) constitutes the initial signal for B-cell activation. This process is involved in anti-viral defence and could have a potential pathogenetic role in autoimmune diseases. This impaired B-cell function presently described represents an immune defect which could be important in the pathogenesis of SS.

The defective in vitro expression of interferon-gamma messenger RNA in rheumatoid arthritis is recovered by cycloheximide.

Circulating T lymphocytes from patients with rheumatoid arthritis (RA) were found to produce low concentrations of interferon-gamma (IFN-gamma) and express low amounts of this messenger RNA (mRNA) in response to stimulation with phytohemagglutinin (PHA). In this study, we have examined the superinduction effect of cycloheximide (CHX) on the IFN-gamma mRNA expression in PHA-stimulated T lymphocytes from nine patients with active RA compared to three healthy individuals. When CHX was added 6 hr postactivation, the expression of IFN-gamma mRNA in RA patients increased significantly at 24 and 48 hr (P less than 0.01) and reached levels similar to those observed in controls. We suggest that posttranscriptional events could play a role in the defective production of IFN-gamma observed in RA.

In vivo interleukin 6 gene expression in the tumoral environment in multiple myeloma.

Whether interleukin 6 (IL 6) is an autocrine or paracrine myeloma cell growth factor in vivo remains unresolved. To identify which cells are producing IL 6 in vivo, we have studied the IL 6 gene expression in bone marrow mononuclear cells (BMMC) of 19 patients with multiple myeloma (MM) and in peripheral blood mononuclear cells (PBMC) of 9 patients with plasma cell leukemia (PCL). We found that the IL 6 gene was transcribed by BMMC of most patients with MM (79%). Further, IL 6 mRNA was not produced by purified myeloma cells from patients with either MM (5 patients) or PCL, but by the bone marrow environment, mainly by monocytes and myeloid cells (CD13+CD15+ cells). For 2 patients with PCL, for whom PBMC and BMMC samples were available, IL 6 mRNA could be detected in BMMC but not in PBMC. Finally, no IL 6 mRNA was detected in five freshly established IL 6-dependent myeloma cell lines. The present data give a clear-cut demonstration of the paracrine origin of IL 6 in vivo in human MM.

[Cerebral vascular accidents in anticoagulant therapy]. / Les accidents vasculaires cérébraux au cours des traitements anticoagulants.

Thirty-three patients hospitalized as they presented with cerebral vascular lesions during anticoagulant therapy (25 intracerebral hemorrhages, 7 subdural hematoma, and one ischemia lesion). Frequency of intra-cerebral hemorrhages along with anticoagulant therapy was about 11 p. 100, this of subdural hematoma ranged from 12 to 38 p. 100. Intra-cerebral hemorrhages failed to show any peculiar topography and volume was variable. A predisposing factor thus existed in about 50 p. 100 of cases: high blood pressure or arterial aneurysm. Previous cranial traumatism was only demonstrated in 48 p. 100 patients presenting with a subdural hematoma. Prognosis as for these intracranial hemorrhages might be compared to this of hemorrhagic lesions appearing under other etiologic conditions. Ischemia lesion was secondary to a severe thrombopenia to heparin.