Jean Philippe Praet

Cyclical pamidronate infusions in postmenopausal osteoporosis

OBJECTIVES Until recently, two bisphosphonates, pamidronate (APD) and etidronate were available for clinical purposes. Contrary to etidronate, pamidronate was not extensively studied in osteoporosis. Therefore, we investigated the effect of cyclic intravenous APD treatment in postmenopausal osteoporosis. METHODS Parameters of bone remodelling and lumbar spine bone mineral density (BMDL) were assessed in 36 postmenopausal women with osteoporosis (BMDL t-score < -2.5). They received five courses of APD. Intervals between courses were defined according to the fasting urinary calcium excretion (UCa/Cr, mg/mg creatinine) which was measured before each APD course and every 2 weeks after the first treatment. The patients were retreated when UCa/Cr had reached baseline levels. Serum biochemical parameters and urinary hydroxyproline (UOHPro/Cr, mg/mg) were measured before each APD. RESULTS UCa/Cr decreased during 21-28 days after each course but UCa/Cr measured before APD infusion remained unchanged. UOHPro/Cr significantly fell after the third APD (P = 0.02). Serum calcium was however not modified. Parameters of bone remodelling decreased with time: bone-GLA protein (BGP) started to fall after the first APD (P = 0.0001) and continued to decrease until the fourth APD course, alkaline phosphatase (ALP) significantly decreased after the first APD (P = 0.005); intact PTH significantly increased at the fifth APD (P = 0.02). BMDL significantly increased after 1 year treatment: +2.9% of baseline value. CONCLUSIONS Cyclical pamidronate treatment of postmenopausal osteoprosis appeared to be effective in reducing bone turnover assessed by BGP, ALP and OHPro/Cr. This effect is followed by an increase in vertebral BMD.

Risk of osteoporosis in men with chronic bronchitis

Theoretically, patients with chronic bronchitis are at risk for osteoporosis. Bone metabolism was assessed in 44 male chronic bronchitics treated with oral prednisolone (C+;n=19) or with bronchodilatory drugs alone (C−;n=25). In both groups, serum osteocalcin was lower (p<0.001) than in age- and sex-matched controls (mean (ng/ml) C+ 1.0, C− 1.9, controls 4.2), while testosterone was at the lower limit of the reference range. Low trabecular bone mineral density (BMD) was noted in the C− group (median Z score −1.0), but both cortical and trabecular BMD were depressed in the C+ group (−1.0 and −1.4, respectively). In conclusion, chronic bronchitics treated with corticosteroids, even at low doses, are at risk for osteoporosis. In both groups, additional factors such as hypogonadism might be responsible for low BMD and low osteocalcin levels. A decrease in bone formation is a possible mechanism of action.

Comparative study of the intestinal absorption of three salts of calcium in young and elderly women

A daily ingestion of 1000 to 1500 mg elemental calcium associated with vitamin D supplement is presently considered to be the adequate and least expensive therapy for senile osteoporosis. There exists only scarce data about calcium absorption with available calcium salts in elderly patients. We have compared the digestive absorption of calcium (Ca) citrate in soluble and solid form and calcium gluconolactate-carbonate in 15 young and 20 elderly, healthy women using the oral calcium loading test. The subjects were divided into two groups. In the first group, the absorption of solid Ca citrate (1000 mg Ca element) was compared to the absorption of Ca gluconolactate-carbonate (1000 mg Ca element) both in young (n=7) and elderly women (n=10). In the second group, the absorption of soluble Ca citrate (1000 mg Ca element) was compared to the absorption of Ca gluconolactate-carbonate (1000 mg Ca element) in young (n=8) and elderly (n=10) women. In the preload phase, basal calciuria was increased in elderly women (p<0.01) although basal calcemia was similar in young and elderly women. After oral administration of the calcium salts, an increase in plasma Ca was observed in both groups which was greater for soluble Ca citrate and Ca gluconolactate than for solid Ca citrate. In young women, the increase in plasma calcium was significantly higher with soluble Ca citrate compared to Ca gluconolactate (p<0.05). In elderly women, the postload calciuria was significantly higher for soluble Ca citrate (p<0.05) and Ca gluconolactate (p<0.05) compared to solid Ca citrate. A similar pattern was observed in young women, although it was not significant. In conclusion, an oral load of 1000 mg soluble Ca citrate and Ca gluconolactate-carbonate induces significant biochemical changes suggesting a better digestive absorption compared to Ca citrate in solid form, both in young and elderly women. We did not observe different response, between young and old patients.

Osteocalcin and bone mineral content in rheumatoid arthritis

SummaryAbnormal bone metabolism was reported in rheumatoid arthritis (RA). In order to evaluate the interest of serum osteocalcin, also called bone GLA- protein (BGP), to assess bone metabolism in RA, we studied 20 postmenopausal RA out- patients and 20 matched controls. Nine patients were treated with low- dose corticosteroids (C+)for at least one year (< 10 mg/day, prednisolone equivalent), the remaining 11 (C−) received non-steroidal anti-inflammatory drugs (NSAID). The distal and proximal forearm bone mineral content (BMC) was measured by single photon absorptiometry, the vertebral BMC was measured by dual photon absorptiometry. A trend to low BGP was observed in the C+ group. The lowest values were observed in patients with vertebral fractures. Compared with controls, both RA groups had similar low significant BMC at the forearm sites. At the vertebral sites, the bone mineral content decrease observed in the two groups, was more marked in the C+ group. From our results, BGP did not appear as a useful index of osteoporosis in RA, except in some patients with vertebral fractures, treated with low-dose corticosteroids.

Oesophageal involvement in rheumatoid arthritis patients : a study with oesophageal radionuclide transit using 81Krm

Rheumatoid arthritis (RA) is an inflammatory disease affecting mainly the joints. In addition, signs of systemic disease are likely to be present although they are not always clinically evident. Oesophageal motility dysfunction, present in 75% of progressive systemic sclerosis patients, was also reported in various other connective tissue diseases. The present study involved 32 rheumatic patients devoid of any gastrointestinal complaints or diseases: 16 RA, nine Raynauds syndrome and seven mild osteoarthritis as controls. Oesophageal transit was assessed by using 81Krm radionuclide scan, a sensitive and non-invasive technique. Diffusing lung capacity for carbon monoxide (DLCO) was performed as evidence of subclinical systemic involvement. Abnormal oesophageal transit was observed in 5/16 RA (31%). Two of them were subsequently discarded due to the presence of asymptomatic goiter and asymptomatic gastrointestinal reflux leaving 3/14 RA for analysis. They all had extra-articular features (EAF) (pericarditis, nodules) and two of them had diminished DLCO. Two with Raynauds syndrome had abnormal oesophageal transit but none of the controls had abnormal oesophageal transit. Upper gastrointestinal dysfunction after exclusion of symptomatic patients appears thus to be not very frequent in RA, even when a sensitive technique is used. Radionuclide transit scanning of the oesophagus is not a more useful method than others in detecting early EAF in RA.

Bone mineral density measured by dual photon and dual energy X-ray absorptiometry: A problem of accuracy

Dual photon absorptiometers (DPA) are currently being replaced by dual energy X-ray absorptiometers (DXA) for measurements of bone mineral density (BMD). In order to evaluate how to use the previously obtained BMD results by DPA (BMDo) in the follow-up of patients, the following study was performed. Ninety-five women who had had BMDo during the last 12 months were selected. L2-L4 BMD was measured twice on the same day using both DPA (BMDp) and by DXA (BMDx). BMDp was highly correlated to BMDx (R=0.95; P<0.001) but a wide variation of the ratio BMDp:BMDx was observed which ranged betweeen 0.65 and 1.09 (mean 0.90, S.D. 0.05). There was no significant relationship between the ratio BDMp:BMDx and age or height but there was a significant relationship between this ratio and the weight of the patient (R=0.31; P<0.001). The results also indicated that the correlation between DXA and DPA was lower than that observed between the two DPA measurements (R=0.98; P<0.001) which, moreover, were not performed on the same day. These observations contrast with the relatively high precision of both instruments and have to be attributed to relative inaccuracy of one or probably both techniques.

Time related bias in longitudinal studies using dual photon absorptiometry

Examining the bone mineral density (BMD’s) slope of patients regularly followed in our department, we observed recently that the group of patients who had their last BMD during the last 6 months of 1989, had a different slope than patients who had their last BMD during the following 6 months. In order to investigate if a small time-related bias of measurement, unsuspected by the former quality control investigations, could exist, we performed the following analyses. A regression equation between BMD and time was calculated and a slope was obtained for 95 women who had been followed for at least 3 yr and had had at least 3 BMD measurements during that time. The women were divided in 3 groups according to when the last BMD measurement had been performed (July–December 1989, January–June 1990 or July–December 1990). The slopes of the 3 groups of patients were compared. For each value of BMD of every patient, a predicted BMD (BMDp) was calculated using the regression equation and the relative difference (RD) between BMDp and BMD was calculated and analysed in relation to time. There was a significant difference (p<0.05) between the slopes of patients in relation to the time when the last BMD had been measured. Significant fluctuations (p<0.001) in RD were observed in relation to time. These RD variations suggested the existence of a time-related error. The presence of this error is also substantiated by the fact that a parallelism existed between the curve of the RD variations and the curve of the mean values of BMD of all patients referred to our department, calculated per period of 4 months. Although the fluctuation of the latter curve was not statistically significant. This study revealed that despite regular quality checkings, an unsuspected not random error may exist. The methodology described in this study can be used as a supplementary long-term quality assessment.