Comparative efficacy and safety study of etidronate and alendronate in postmenopausal osteoporosis. effect of adding hormone replacement therapy.

OBJECTIVES: To compare the efficacy and safety of etidronate and alendronate in patients with postmenopausal osteoporosis and to assess the efficacy of either bisphosphonate in combination with hormone replacement therapy (HRT). PATIENTS AND METHODS: In this pragmatic study, the main efficacy criterion was the mean annual change in bone mineral density (BMD). Patients who had a past or current history of etidronate or alendronate treatment for postmenopausal osteoporosis with at least 18 months follow-up and an evaluation in 1999 were eligible. Recruitment was in an outpatient clinic with a special focus on metabolic bone diseases. Osteoporosis was defined as at least one low-energy fracture or as a lumbar spine or femoral neck BMD decrease to at least 2.5 SD below the mean in young women. HRT was not an exclusion criterion provided treatment duration was longer than 1 year. Etidronate was given cyclically (14-day courses in a dosage of 400 mg/d separated by 76-day intervals with calcium and vitamin D supplementation) and alendronate was given daily in a dosage of 10 mg/d. RESULTS: Of the 99 patients who met our inclusion criteria, 53 received etidronate (including 23 on HRT) and 46 alendronate (18 on HRT). Repeat BMD measurements were obtained in 88 patients, including 11 who stopped their bisphosphonate therapy within the first year of use because of adverse events. Lumbar spine BMD (mean +/- SD) increased significantly both in the etidronate group (+2.1% +/- 0.7%/year) and in the alendronate group (+5.3% +/- 0.9%/year). The increase was significantly greater with alendronate (P< 0.01). The lumbar spine BMD increase was largest in the patients on alendronate and HRT (+6.5% +/- 1.4%/year) and was smallest (and nonsignificant) in the patients on etidronate without HRT (+ 1.2% +/- 0.8%). Femoral neck BMD showed no significant changes in any group. In the intention-to-treat analysis, fractures occurred in 12 etidronate patients (22.6%) and six (13.0%) alendronate patients (nonsignificant). Adverse events requiring bisphosphonate discontinuation before the scheduled date of the follow-up BMD measurement occurred in one patient (1.9%) in the etidronate group (generalized osteomalacia) and in ten patients (21.7%) in the alendronate group (upper or lower gastrointestinal tract symptoms in six and four patients, respectively; P < 0.01). CONCLUSION: Both etidronate and alendronate significantly increased lumbar BMD, but the effect was significantly more marked with alendronate. Conversely, adverse effects, most notably gastrointestinal symptoms, were more common with alendronate, so that premature treatment discontinuation because of adverse events were more common in the alendronate group. Both differences should be taken into account when selecting the best drug for a patient with postmenopausal osteoporosis.

Management of male osteoporosis.

UNLABELLED: The objective of this study was to evaluate the efficacy of treatments for male osteoporosis selected based on the cause of the disease. METHODS: Sixty-three men with osteoporosis (T-score at the lumbar spine and/or femoral neck lower than -2.5) with a mean age of 53+/-11 years were studied. Forty-three (68.3%) had a history of fracturing without trauma (vertebral fractures, 37 patients, 57%). Treatments were as follows: idiopathic osteoporosis: calcium and vitamin D supplements (N = 10) or cyclical etidronate for 2 weeks followed by calcium and vitamin D supplements for 76 days (N = 29); moderate idiopathic phosphate diabetes: calcitriol and phosphate (N = 15); idiopathic hypercalciuria: hydrochlorothiazide (N = 6); and hypogonadism: testosterone (N = 3). RESULTS: Percentage change in bone mineral density (mean +/- standard error of the mean) after 18 months: calcium and vitamin D (lumbar spine: 0.6+/-2; femoral neck: 2.2+/-2.2); etidronate (lumbar spine: 3.6+/-1.4*; femoral neck: 0.5+/-1); calcitriol (lumbar spine: 7.0+/-3.5*; femoral neck: 0.0+/-1.4); thiazide diuretic (lumbar spine: 1+/-3.2; femoral neck: -2.3+/-3.7); and testosterone (lumbar spine: 6.8+/-6.4; femoral neck: 2.5+/-2.7), where *P < 0.05 versus baseline. Gastrointestinal side effects occurred in three patients (4.8%), including two on calcitriol-phosphate therapy and one on etidronate therapy. Of the six (9.5%) patients who experienced incident fractures, four were on etidronate, one on calcitriol-phosphate, and one on calcium-vitamin D. No patients discontinued their treatment because of side effects. CONCLUSION: Etidronate and the combination of calcitriol-phosphate produce a significant increase in lumbar spine bone mass in men with idiopathic osteoporosis or moderate idiopathic phosphate diabetes.

[Chronotherapy of tenoxicam]. / Chronothérapie du ténoxicam.

A study was carried out in order to investigate the chronotherapy (dosing time dependency) of an NSAID, the tenoxicam administered in ankylosing spondylitis, rheumatoid arthritis and osteoarthritis of the hip. These variations in efficacy exist as much for pain as for stiffness and maximum efficacy is obtained with administration at 8 am or 12 pm. Since the tolerance was good, we recommend midday as an optimal once-a-day dosing time.

[Bone effects of hypothyroidism in adults. Apropos of 20 cases]. / Le retentissement osseux de l'hypothyroïdie chez l'adulte. A propos de 20 observations.

In contrast to the complications of hyperthyroidism, the bone lesions associated with hypothyroidism have not been extensively studied. A prospective study was conducted in 20 adults with protothyroid acquired hypothyroidism did not reveal any abnormalities in the parameters of phospho-calcium metabolism or the concentrations of PTH and the metabolites of vitamin D. The histomorphometric study of bone revealed hyperosteoidosis reflected by a considerable increase in the index of thickness of the osteoid, essentially affecting the relative osteoid volume. The surfaces of resorption and the bony trabecular volume were within normal limits and the rate of calcification was slightly decreased. The modifications of the histomorphometric investigation can be interpreted as a consequence of the slowing down of the basal osseous activity (BMR) due to thyroid hormone deprivation.

[Phospho-calcium metabolism and bone histomorphometry in chronic alcoholism. Apropos of 25 cases]. / Métabolisme phosphocalcique et histomorphométrie osseuse dans l'éthylisme chronique. A propos de 25 cas.

Twenty five subjects, chronic alcoholics for more than five years, without any past history or clinical signs of portal hypertension or oedemato-ictero-ascitic decompensation, were examined by laboratory tests reflecting phosphoro-calcium metabolism and by transiliac bone biopsy with histomorphometric examination of nondecalcified bone. The subjects were fairly homogeneous in terms of liver function and liver disease, when present, was only minimal. The phosphoro-calcium parameters were generally normal, but hypomagnesaemia was observed. On the other hand, the histomorphometric study often revealed marked alterations: hyperosteoidosis: raised index of osteoid thickness (IOT) in 15 of the 25 cases, increase in the relative osteoid volume (ROV) in 12 cases and increase in the osteoid area (OA) in 8 cases. The bony trabecular volume (BTV) was only mildly reduced (13 out of 24) and there was increased resorption, reflected by an increase in the area of resorption (AR) seen in 15 cases, associated with a moderate increase in the area of periosteocytic lacunae (APOL). The essential changes consist of hyperosteoidosis with morphological osteomalacia in 60% of cases and reduction of the trabecular volume in 54%. Comparison of the different parameters reveals the following histomorphometric profile: BTV; AR; ROV; OA; IOT; APOL. Thus, histological bone changes occur in chronic alcholics before the appearance of signs of liver failure. These quantitatively minor changes are suggestive deficiency type bone.

[Bone and phosphoro-calcium metabolism in reflex sympathetic dystrophy]. / L'os et le métabolisme phosphocalcique dans l'algodystrophie.

A combined study organised by the French Society of Rheumatology was devoted to the investigation of bone and phosphoro-calcium metabolism in cases of reflex sympathetic dystrophy. The following observations were made: the usual phosphoro-calcium parameters are not altered, apart from a slight elevation of the urinary calcium in multifocal forms of the disease, during the 3rd and 4th months; the level of PTH, studied in 11 patients, was normal in each case; the examination of 8 bone biopsies, one performed in the 7th week and six others performed during the 3rd and 4th months of the disease, showed, initially, invasion of the spongy tissue by oedema, signs of marrow stress and bone stress, with a reduction in the number of osteoblasts, without any marked alteration of bone remodelling. At a later stage, the biopsy shows intense bone remodelling with hyperosteoclastosis and hyperosteoblastosis and the formation of irregular bone tissue which later becomes lamellar. Electron microscopic study of two biopsies revealed signs of acellular demineralisation with normal appearance of the osteoblasts and osteoclasts.

[Further observations on the presence of iron in the articuler synovial membrane]. / Secondes vues sur la présence de fer dans la synoviale articulaire

In 1971, a study of 66 synovial biopsy samples indicated that the presence of ferric deposits in the subintimal synovial tissue was of real semiological value in the diagnosis of rheumatoid synovitis. In 1975, a study of 228 synovial biopsy samples led the authors to reconsider this finding: the presence of ferric deposits in the subintimal synovial tissue was far from being a constant feature in rheumatoid synovitis and it was seen with similar frequency in other forms of chronic inflammatory rheumatism and also in several other joint conditions. The origin of the synovial iron and the influence it may have on the development of the rheumatoid processes remain obscure.