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Biomedical subjects

D Thiébaud

Publications and source records attributed to D Thiébaud.

At least 19 recordsLinked to original sources
PubMed2003

Long term effects of a single dose of intravenous Ibandronate.

For defining the optimal regimen of a treatment of osteoporosis with an intravenous bisphosphonate one needs to know the duration of action of a single dose of the given drug. This allows us to establish the frequency by which a given dose has to be administered for obtaining a sufficient suppression of bone resorption over a longer period. In this study 1 and 2 mg Ibandronate were given as a single i.v. injection to young normal men and to healthy postmenopausal women on a free diet and with no treatment or supplements, and the markers of bone metabolism, as well as BMD, were followed for 6 months. Urinary C-telopeptides decreased by 81-95% 1 week after the injection and remained significantly decreased for 2 weeks after 1 mg Ibandronate, and for 4 months after 2 mg. In men, PTH increased by 80% at one week and remained significantly increased for 2 weeks, after 1mg and 2 mg Ibandronate. Plasma osteocalcin decreased slowly over 2 months in all 3 groups by 22%. Alkaline phosphatase showed similar, but not significant changes. In conclusion, the inhibition of bone resorption induced by 1 mg Ibandronate i.v. does not exceed 1 month and does not allow 3 month intervals in the treatment of osteoporosis, while 2 mg cover 3 months at least.

Journal Article↗
PubMed2001

Intravenous pamidronate as treatment for osteoporosis after heart transplantation: a prospective study.

Fractures due to osteoporosis are one of the major complications after heart transplantation, occurring mostly during the first 6 months after the graft, with an incidence ranging from 18% to 50% for vertebral fractures. Bone mineral density (BMD) decreases dramatically following the graft, at trabecular sites as well as cortical sites. This is explained by the relatively high doses of glucocorticoids used during the months following the graft, and by a long-term increase of bone turnover which is probably due to cyclosporine. There is some evidence for a beneficial effect on BMD of antiresorptive treatments after heart transplantation. The aim of this study was to assess prospectively the effect on BMD of a 3-year treatment of quarterly infusions of 60 mg of pamidronate, combined with 1 g calcium and 1000 U vitamin D per day, in osteoporotic heart transplant recipients, and that of a treatment with calcium and vitamin D in heart transplant recipients with no osteoporosis. BMD of the lumbar spine and the femoral neck was measured by dual-energy X-ray absorptiometry in all patients every 6 months for 2 years and after 3 years. Seventeen patients, (1 woman, 16 men) aged 46+/-4 years (mean +/- SEM) received only calcium and vitamin D. A significant decrease in BMD was observed after 6 months following the graft, at the lumbar spine (- 6.6%) as well as at the femoral neck (-7.8%). After 2 years, BMD tended to recover at the lumbar spine, whereas the loss persisted after 3 years at the femoral neck. Eleven patients (1 woman and 10 men) aged 46+/-4 years (mean +/- SEM) started treatment with pamidronate on average 6 months after the graft, because they had osteoporosis of the lumbar spine and/or femoral neck (BMD T-score below -2.5 SD). Over the whole treatment period, a continuous increase in BMD at the lumbar spine was noticed, reaching 18.3% after 3 years (14.3% compared with the BMD at the time of the graft). BMD at the femoral neck was lowered in the first year by -3.4%, but recovered totally after 3 years of treatment. In conclusion, a 3-year study of treatment with pamidronate given every 3 months to patients with existing osteoporosis led to a significant increase in lumbar spine BMD and prevented loss at the femoral neck. However, since some of these patients were treated up to 14 months after the transplant, they may already have passed through the phase of most rapid bone loss. In patients who were not osteoporotic at baseline, treatment with calcium and vitamin D alone was not able to prevent the rapid bone loss that occurs immediately after transplantation.

Bone Density↗
PubMed1999

Effect of supplementation with vitamin D3 and calcium on quantitative ultrasound of bone in elderly institutionalized women: a longitudinal study.

Supplementation of elderly institutionalized women with vitamin D and calcium decreased hip fractures and increased hip bone mineral density. Quantitative ultrasound (QUS) measurements can be performed in nursing homes, and easily repeated for follow-up. However, the effect of the correction of vitamin D deficiency on QUS parameters is not known. Therefore, 248 institutionalized women aged 62-98 years were included in a 2-year open controlled study. They were randomized into a treated group (n = 124), receiving 440 IU of vitamin D3 combined with 500 mg calcium (1250 mg calcium carbonate, Novartis) twice daily, and a control group (n = 124). One hundred and three women (42%), aged 84.5 +/- 7.5 years, completed the study: 50 in the treated group, 53 in the controls. QUS of the calcaneus, which measures BUA (broadband ultrasound attenuation) and SOS (speed of sound), and biochemical analysis were performed before and after 1 and 2 years of treatment. Only the results of the women with a complete follow-up were taken into account. Both groups had low initial mean serum 25-hydroxyvitamin D levels (11.9 +/- 1.2 and 11.7 +/- 1.2 micrograms/l; normal range 6.4-40.2 micrograms/l) and normal mean serum parathyroid hormone (PTH) levels (43.1 +/- 3.2 and 44.6 +/- 3.5 ng/l; normal range 10-70 ng/l, normal mean 31.8 +/- 2.3 ng/l). The treatment led to a correction of the metabolic disturbances, with an increase in 25-hydroxyvitamin D by 123% (p < 0.01) and a decrease in PTH by 18% (p < 0.05) and of alkaline phosphatase by 15% (p < 0.01). In the controls there was a worsening of the hypovitaminosis D, with a decrease of 25-hydroxyvitamin D by 51% (p < 0.01) and an increase in PTH by 51% (p < 0.01), while the serum calcium level decreased by only 2% (p < 0.01). After 2 years of treatment BUA increased significantly by 1.6% in the treated group (p < 0.05), and decreased by 2.3% in the controls (p < 0.01). Therefore, the difference in BUA between the treated subjects and the controls (3.9%) was significant after 2 years (p < 0.01). However, SOS decreased by the same amount in both groups (approximately 0.5%). In conclusion, BUA, but not SOS, reflected the positive effect on bone of supplementation with calcium and vitamin D3 in a population of elderly institutionalized women.

Aged↗
PubMed1999

Serum parathyroid hormone-related protein levels and response to bisphosphonate treatment in hypercalcemia of malignancy.

The pathogenesis of hypercalcemia of malignancy comprises increased net bone resorption and enhanced renal tubular reabsorption of calcium (Ca). To evaluate the prevalence of an increased renal tubular reabsorption of Ca index [tubular reabsorption of calcium index (TRCaI)] in cancer patients with hypercalcemia and of elevated circulating levels of PTH-related protein (PTHrP), which is recognized as a major mediator of this syndrome, we investigated 315 well rehydrated patients, aged 58.1 +/- 0.7 yr (mean +/- SEM), with hypercalcemia [albumin-corrected plasma Ca (pCa), >2.7 mmol/L] secondary to histologically proven malignancy. Changes in pCa and, therefore, various Ca filtered loads were obtained by different degrees of bone resorption inhibition achieved with a single infusion of the bisphosphonate ibandronate, given at various doses on a randomized, double blind basis. PTHrP was determined at baseline in 147 of the patients and 7 days after bisphosphonate therapy in 73. Before ibandronate therapy, pCa was 3.36 +/- 0.02 mmol/L, mean TRCaI was increased at 3.09 +/- 0.03 mmol/L glomerular filtration rate (GFR; normal, 2.40-2.90), and 65% of patients had TRCaI above 2.90 mmol/L GFR. Mean serum PTHrP levels were 4.9 +/- 0.5 pmol/L (normal, <2.5) and values above the normal range were found in 53% of the patients (76% in lung and upper respiratory tract malignancies). By 7 days after the infusion of ibandronate, a decrease in pCa of 0.69 +/- 0.03 mmol/L (20.0 +/- 0.7%; P < 0.001) and in bone resorption [mean change in fasting urinary Ca, 0.09 +/- 0.04 mmol/L GFR (47.6 +/- 8.6%; P < 0.001) and 14.4 +/- 1.7 nmol/mmol (27.6 +/- 10.6%; P < 0.01) in deoxypyridinoline] was observed. TRCaI was slightly lowered by 0.30 +/- 0.09 mmol/L GFR. Mean changes in PTHrP, 1,25-dihydroxyvitamin D3, and PTH were +0.7 +/- 0.4 (P = NS), +27.6 +/- 3.0 (P < 0.001), and +2.9 +/- 0.8 (P < 0.005) pmol/L, respectively. After ibandronate treatment, the relative risk of relapsing hypercalcemia was particularly increased (3.43-fold) in lung and upper respiratory tract malignancies. These results obtained in a large cohort of patients indicate a significant prevalence of an increased renal tubular reabsorption of calcium index in hypercalcemia of malignancy and a substantial proportion of patients with detectable PTHrP.

Absorption↗
PubMed1998

Influence of anthropometric parameters and biochemical markers of bone metabolism on quantitative ultrasound of bone in the institutionalized elderly.

The assessment of bone quality by quantitative ultrasound (QUS), a transportable and relatively cheap method, shows some correlations with bone mineral density (BMD) as measured by dual-energy X-ray absorptiometry (DXA) and with fracture risk. To examine its correlation with bone metabolism in a population of institutionalized elderly people known to be at high risk for vitamin D deficiency and secondary hyperparathyroidism, QUS of the calcaneus and biochemical parameters were measured in 264 women aged 85 +/- 7 (SD) years and in 103 men aged 81 +/- 8 years living in 19 nursing homes. Vitamin D deficiency was frequent in this population: 41.9% of the women and 31.4% of the men had a serum 25-hydroxyvitamin (25OHD) level below the 2.5th percentile level of 3276 normal Swiss adults (6.2 micrograms/l or 15.5 mmol/l). Hyperparathyroidism was less frequent: serum parathyroid hormone (PTH) levels were above the 97.5th percentile level of normal adults (70 pg/l) in 18.9% of women and 9.8% of men. In women, QUS data correlated significantly with age (r = -0.297), body mass index (BMI) (r = 0.403), calcium (r = 0.220), PTH (r = -0.296), 25OHD (r = 0.298) and alkaline phosphatase (AP) (r = -0.170) for broadband ultrasound attenuation (BUA), and with age (r = -0.195), BMI (r = 0.208), PTH (r = -0.174), 25OHD (r = 0.140) and AP (r = -0.130) for speed of sound (SOS). In men, ultrasound data correlated with BMI (r = 0.326), calcium (r = 0.199), 25OHD (r = 0.258) and AP (r = -0.311) for BUA, and with AP (r = -0.196) for SOS. In women, but not in men because of their smaller number, a multivariate analysis was performed to examine relationships between age, BMI, biochemical markers and QUS. Age, BMI, PTH and phosphate explained 30% of the variance of BUA and 10% for SOS. In conclusion, QUS of bone evaluates characteristics of bone that are influenced, at least partially, by age, BMI and the secondary hyperparathyroidism due to vitamin D deficiency.

Age Factors↗
PubMed1998

A 3-year study of prevention of postmenopausal bone loss: conjugated equine estrogens plus medroxyprogesterone acetate versus tibolone.

The aim of this study was to investigate the effects of tibolone in the prevention of postmenopausal bone loss over 3 years, and to compare these with the effects of sequential hormone replacement therapy. Forty early postmenopausal women were randomized to a 21-day regimen of conjugated equine estrogens (CEE, Premarin) plus sequential medroxyprogesterone acetate (MPA, Prodafem), or tibolone (Livial) daily. In total, 36 women completed 12 months and were considered for the intent-to-treat analysis, 34 completed 24 months and 23 completed 36 months. Main drop-out reasons were: lost to follow-up (n = 9) and minor side-effects (n = 4). Bone mineral density was measured at baseline and after 6, 12, 24 and 36 months, using dual-energy X-ray absorptiometry at the lumbar spine and the upper femur (neck, trochanter, total hip). In both groups, bone loss was prevented. Treatment with tibolone demonstrated significant increases in bone density at the spine (+4.6%; p < 0.01), at the total hip (+3.2%; p < 0.01) and at the trochanter (+4.5%; p < 0.01), whereas the CEE/MPA group showed a non-significant increase of bone mineral density at the lumbar spine (+2.6%) but no increases at the hip. Between-group differences in bone mineral density changes were significant (p < 0.05) for the total hip and the trochanter at 36 months. This increase of bone mineral density was not accompanied by changes in insulin-like growth factor-I (IGF-I) or insulin-like growth factor binding protein-3 (IGFBP-3) in either group. Osteocalcin, alkaline phosphatase and urinary ratios of hydroxyproline/creatinine and calcium/creatinine significantly decreased in both groups. In conclusion, sequential CEE/MPA prevented cortical and trabecular bone loss, with a transient increase of bone mineral density only during the first 6 months. Tibolone not only prevented cortical and trabecular bone loss, but further increased bone mineral density at the lumbar spine and at the hip throughout the 3 years of treatment, suggesting a sustained positive effect on bone mass.

Absorptiometry, Photon↗
PubMed1997

Bone resorption in multiple myeloma and in monoclonal gammopathy of undetermined significance: quantification by urinary pyridinium cross-links of collagen.

To quantify osseous breakdown in multiple myeloma (MM), monoclonal gammopathy of undetermined significance (MGUS), and benign osteoporosis, we measured urinary levels of pyridinium cross-links of collagen in 50 patients with newly diagnosed and untreated MM, 40 patients with MGUS, 40 untreated patients with osteoporotic vertebral fractures, and 64 healthy adults. Ion-paired, reverse-phase high-performance liquid chromatography (HPLC) was used to measure total urinary excretion of pyridinoline (h-PYD) and deoxypyridinoline (h-DPD). Urinary excretion of free immunoreactive deoxypyridinoline (i-DPD) was determined with an enzyme immunoassay. MM patients had significantly (P < .0001) higher levels of h-PYD, h-DPD, and i-DPD than the healthy adults, patients with MGUS, or patients with osteoporosis. The MGUS and osteoporosis groups presented with elevated (P < .05) levels of urinary pyridinium cross-links when compared with healthy controls. In 20 MM patients who subsequently received chemotherapy, the percent changes in i-DPD did not correlate with the changes in the monoclonal protein. In one of three patients experiencing a transition of initial MGUS into stage I MM, i-DPD increased above the upper limit of the normal range. In 13 patients with stable MGUS, i-DPD remained normal in repeated measurements. Based on the upper limits of the normal range, the sensitivity of urinary pyridinium cross-links in stage I and II MM was low (<50%), but it was between 78% (h-DPD) and 93% (i-DPD) in stage III MM. Specificity in patients with MGUS was between 87% (h-PYD) and 97% (h-DPD). In conclusion, determining the urinary excretion of pyridinium cross-links seems to be a promising noninvasive and thus easily repeatable method for evaluating the actual degree of osseous breakdown. Although measurement of pyridinium cross-link levels is not useful in discriminating patients with MGUS from early-stage myeloma patients, determination of i-DPD levels may contribute importantly to clinical guidance, since increased i-DPD levels seem to identify patients who are particularly likely to benefit from osteoclast-inhibiting drugs such as bisphosphonates. The fact that in a number of patients paraprotein concentrations and i-DPD levels did not change in parallel but instead diverged strongly after chemotherapy might explain the observation that bone lesions sometimes progress even in patients who achieve complete remission.

Adult↗
PubMed1997

Importance of albumin, 25(OH)-vitamin D and IGFBP-3 as risk factors in elderly women and men with hip fracture.

The relative importance of vitamin D deficiency, secondary hyperparathyroidism, nutritional deficiency and low bone mineral density (BMD) as risk factors for hip fracture is not definitely established. In the framework of a case-control study of risk factors for hip fractures, biochemical markers of bone metabolism and nutrition and femoral BMD data were compared in 136 female and 43 male hip fracture patients, 136 female and 44 male age-matched hospitalized controls, and 47 healthy elderly women (8 men). Patients with hip fracture had lower albumin (-10%) and 25(OH)-vitamin D (25(OH)D; -19%) compared with hospitalized controls, and lower albumin (-28%) and 25(OH)D levels (-52%) compared with the elderly controls. Serum values of IGFBP-3 were also significantly lower (-33%) in hip fracture patients than in community controls. BMD of femoral neck was lower (p < 0.001) in patients than in hospitalized and community controls. In hip fracture patients, parathyroid hormone (PTH) correlated weakly with BMD (neck: r = -0.19, trochanter: r = -0.17; both p < 0.05). When all women were pooled (n = 233), albumin correlated significantly (age-adjusted) with BMD at all sites (neck: r = 0.27, trochanter: r = 0.25; all p < 0.001). Albumin, but not 25(OH)D, also correlated with skinfold thickness (r = 0.19, p < 0.0025) and with body mass index (BMI) (r = 0.14, p < 0.05). Male patients with hip fracture had lower BMD and albumin (both p < 0.001), 25(OH)D (p = 0.02) and IGFBP-3 levels (p < 0.005) compared with the controls. When male patients and controls were pooled together, albumin, skinfold thickness and BMI were significantly correlated with each other, but not with BMD. IGFBP-3 was highly correlated with albumin (p < 0.0001), 25(OH)D (p < 0.005) and, less significantly, with PTH (p < 0.05), but not with BMI or skinfold thickness. IGFBP-3 was significantly correlated with BMD at all sites (neck: r = 0.27, p < 0.05; trochanter: r = 0.40, p < 0.0005). In conclusion, low albumin and low BMD were both important risk factors for hip fracture. Low serum albumin was the strongest independent variable correlated with hip fractures. In men. IGFBP-3 was correlated with BMD. The femoral BMD depended only weakly on PTH and 25(OH)D, but was correlated at all sites with albumin, a non-specific parameter of nutrition and general health.

Aged↗
PubMed1997

An in vitro and in vivo study of cytokines in the acute-phase response associated with bisphosphonates.

We studied the acute phase response, including specific cytokine production, [interleukin-1 (IL-1), interleukin-6 (IL-6), tumor necrosis factor alpha(TNF alpha)] following a single dose of Aredia (disodium pamidronate) in patients with increased bone turnover and, in vitro, the role played by specific cytokines in the acute-phase reaction which may follow the administration of aminobisphosphonates. An in vivo exploratory study was done on 24 in- and outpatients with increased bone turnover given a single intravenous dose of pamidronate 60 mg. Measurements were taken at baseline and at 24, 48, and 72 hours. The main outcome measures were changes from baseline in serum IL-1, IL-6, and TNF alpha. In addition, C-reactive protein (CRP), white blood cell count (WCC), lymphocyte count, and elastase concentration were measured. Symptomatic evaluation was made of fever, bone pain, and rigors. In vitro, whole blood from eight healthy volunteers was exposed to various concentrations of the three bisphosphonates--pamidronate, clodronate, and zoledronate. Measurements were taken immediately before and at 3, 6, and 10 hours after exposure to drugs. The main outcome measures were changes in serum IL-1, IL-6, and TNF alpha. In vivo, there was a statistically significant (P < 0.001) increase in median values of TNF alpha in all post-baseline measurements. Median values for IL-6 also showed a significant (P < 0.001) increase at 24 hours after dosing. There were no statistically significant changes in median IL-1 values. Few patients showed any change from baseline in total WCC or in lymphocyte count, but 62.5% of patients with normal range baseline values for CRP increased to above normal levels after treatment. Fourteen patients experienced fever; 2 reported rigors. There was no correlation between fever and changes in cytokines. There were no serious adverse experiences or premature discontinuations due to poor tolerability, and 91% of the patients expressed willingness to receive pamidronate again. In vitro, an increase in TNF alpha and a mild increase in IL-6 was seen with all bisphosphonates, with the greatest effects seen with the highest concentration of both pamidronate and zoledronate. No changes were observed in IL-1 with any agent. Significant changes in both TNF alpha and IL-6 were observed within 3 days of a single dose of pamidronate in patients treated for the first time confirming previous findings. However, the lack of change in IL-1 in vivo and in vitro does not support the hypothesis that this cytokine plays a major role in the acute phase reaction. The cellular mechanism of the interaction among aminobisphosphonates, IL-6, and TNF alpha requires further investigations. The results of the in vitro study are consistent with the in vivo findings.

Acute-Phase Reaction↗
PubMed1997

Three monthly intravenous injections of ibandronate in the treatment of postmenopausal osteoporosis.

PURPOSE: Oral treatment of osteoporosis with bisphosphonates relies on compliance, the absorption being low and suppressed by simultaneous food intake. Intravenous (IV) treatment with an aminobisphosphonate, pamidronate (once every 3 months) was effective, but required infusions. Ibandronate, a new very potent aminobisphosphonate, can be administered safely as an IV bolus injection, and therefore offers an interesting alternative suitable for outpatient treatment. PATIENTS AND METHODS: To test the efficacy of this bolus IV treatment in postmenopausal osteoporosis in randomized partly double-blind, placebo controlled study, 125 postmenopausal women (mean age, 64 years) with osteoporosis (bone mineral density [BMD] < -2.5 SD T score) received a placebo or ibandronate (0.25, 0.5, 1, or 2 mg) every 3 months. All patients received 1 g calcium/day. BMD, in g/cm2, was measured by dual-energy x-ray absorptiometry at all standard sites. RESULTS: Lumbar spine BMD (L2 to L4) did not change (0.85%) in the placebo group, but increased by 2.4%, 3.5%, 3.7%, and 5.2% at 12 months for dose-ranging groups (no significant differences among ibandronate groups). The increase was statistically significantly different from placebo for the 0.5 mg (P < 0.006), 1 mg (P < 0.004), and 2 mg (P < 0.001) group, whereas with 0.25 mg no significant differences occured. After 1 year there were no significant changes in BMD compared with placebo at the femoral neck, Ward's triangle, and distal forearm. Total hip and trochanter BMD increased significantly, by 1.8% and 2.9% for total hip and by 2.7% and 4.2% for trochanter in the 1 and 2 mg group, respectively. Urinary excretion of C-telopeptide and N-telopeptide decreased after 1 month in all ibandronate groups, with a clear dose dependency. Three months after the first injection of 2 mg ibandronate there was still a significant reduction in these markers of bone resorption. Osteocalcin decreased progressively and dose dependently over time. There was a correlation between the decrease in C-telopeptide measured after 1 month and the increase in lumbar spine BMD after 1 year (n = 115, r = -0.26, P < 0.012). Ibandronate therapy proved to be safe. There was no significant difference in the overall number of adverse events in the ibandronate groups compared with the placebo group. Considering specific adverse events, no dose dependency and difference to placebo could be observed apart from acute reactions that occurred in 7% of the patients. CONCLUSION: Treatment of postmenopausal osteoporosis by interval IV bolus injections of the bisphosphonate ibandronate was safe and effective in increasing BMD through a dose-dependent inhibition of bone resorption. The high potency of ibandronate allows 3-month interval bolus IV injections as a new therapeutic approach with optimal compliance.

Absorptiometry, Photon↗
PubMed1997

Dose-response study of ibandronate in the treatment of cancer-associated hypercalcaemia.

Hypercalcaemia is an important cause of morbidity in malignant disease. We studied the efficacy and safety of intravenous ibandronate (a new, potent bisphosphonate) in a multicentre study of 147 patients with severe cancer-associated hypercalcaemia which had been resistant to treatment with rehydration alone. Of 131 randomized patients who were eligible for evaluation, 45 were allocated to receive 2 mg ibandronate, 44 patients to receive 4 mg and 42 patients to receive 6 mg. Serum calcium values fell progressively in each group from day 2, reaching a nadir at day 5, and in some patients normocalcaemia was maintained for up to 36 days after treatment. The 2-mg dose was significantly less effective than the 4-mg or 6-mg dose in correcting hypercalcaemia, as the number of patients who achieved serum calcium values below 2.7 mM after treatment was 50% in the 2-mg group compared with 75.6% in the 4-mg group and 77.4% in the 6-mg group (P < 0.05; 2 mg vs others). In a logistic regression analysis, three factors were found to predict response; ibandronate dose (higher doses were more effective), severity of presenting hypercalcaemia (severe hypercalcaemia was associated with less complete response) and tumour type (patients with breast carcinoma and haematological tumours responded better than those with other tumours). Ibandronate was generally well tolerated and no serious drug-related adverse events were observed. We conclude that ibandronate is a safe, well tolerated and effective treatment for cancer-associated hypercalcaemia, which should prove a useful addition to the current range of therapies available to treat this condition.

Bone Resorption↗
PubMed1996

[Importance of the clinical profile in the postmenopausal osteoporosis screening by densitometry].

In order to test the impact of a given risk profile on the incidence of osteoporosis which could justify BMD measurement, and that of a low risk profile which could render it unnecessary, BMD was measured in 217 women under 72 in whom menopause had occurred at least 6 years previously and who corresponded to one of the two following profiles: high risk (A, n = 102) = BMI < 27 kg/m2, with no estrogen replacement treatment, and with at least one of the following risk factors: BMI < 20, early menopause, positive family history, no dairy products associated with tobacco consumption (> 10 cigarettes/day for > 20 years and/or alcohol consumption of > 0.5 l wine/day during > 10 years, corticotherapy of > 6 months, rickets, anorexia nervosa. Low risk (B, n = 115) = absence of characteristics of group A, BMI > 27 kg/m2 with (B+, n = 24) or without estrogen therapy (B-, n = 91). BMD was measured by DXA in 4 centers using Lunar or Hologic equipment. Results were expressed in % of the mean of the respective young adult control groups. As expected, BMD was significantly different in these two subgroups of the population. Osteoporosis was diagnosed (BMD < 75% = < -2.5 SD, according to WHO) in 72% of group A, and in 17% (B+) and 19% (B-) respectively of group B. There was no difference between the various risk factors in group A concerning their impact on BMD, but concerning incidence, low BMI and early menopause were the most frequent. The high risk profile of group A seems to justify densitometry, since it leads to the diagnosis of osteoporosis in over 70%. However, the protective profile of group B does not exclude osteoporosis (risk still 20%); only in severe obesity (BMI > 33) does it drop to 1%.

Absorptiometry, Photon↗
PubMed1996

[Evaluation of bones using quantitative ultrasonography].

The evaluation of bone by ultrasound is a new, transportable and non-irradiating method. It measures attenuation of ultrasound (BUA), as well as velocity (SOS) of ultrasound in a given tissue. For the measurement of bone, the most frequently used bone is the calcaneus. We have used this technique (Achilles, Lunar) to evaluate the reproducibility of measurements in healthy volunteers and to determine the correlations between the results of ultrasound measurements and those of conventional densitometry (DXA) in a population of postmenopausal females who consulted for screening or diagnosis of osteoporosis. Although several publications have already dealt with the same questions, it is important to reexamine them locally before the technique is uncritically used even in unspecialized centers. The coefficients of variation corresponded to that reported by others: 1.8% for BUA and 0.3% for SOS. The correlations between the ultrasound measurements and the results of DXA at lumbar spine, femoral neck and calcaneus in 57 postmenopausal women aged +/- 59 (43-78) years and in part osteoporotic (DXA results below 2.5 SD-T-score) (Hologic QDR 2000) were all significant (p < 0.001). The best correlation between the two techniques (DEXA and ultrasound) is found when applied to the same site, i.e. the calcaneus (r > 0.8). These results also agree with the literature. Low ultrasound values (BUA < 100 dB/MHz, SOS < 1495 m/s) are highly suggestive of osteoporosis, while high ultrasound values are almost exclusively found in non-osteoporotic women. This information provides the basis for further investigations, such as correlation with fracture risk, in cross-sectional and longitudinal studies.

Absorptiometry, Photon↗
PubMed1996

Quantitative ultrasound of bone in institutionalized elderly women: a cross-sectional and longitudinal study.

Quantitative ultrasound of bone is a promising method for bone assessment: radiation-free, portable and predictive of hip fracture. Its portability allowed us to study the relationships between ultrasonic parameters of bone with age and with non-vertebral fractures in elderly women living in 19 nursing homes. Broadband ultrasound attenuation (BUA) and speed of sound (SOS) of the calcaneus were measured (and the stiffness index calculated) in a sample of 270 institutionalized women, aged 85 +/- 7 years, using an Achilles bone densitometer (Lunar). The effects of age, history of non-vertebral and non-traumatic fractures, body mass index, triceps skinfold and arm circumference were assessed on BUA, SOS and stiffness index. Furthermore, to evaluate longitudinally the influence of aging on the ultrasound parameters of bone, 60 subjects from the same group had a second ultrasound measurement after 1 year. The cross-sectional analysis of the data on all 270 women showed a significant decrease (p < 0.001) with age in BUA, SOS and stiffness index (-0.47%, -0.06%, and -1.01% respectively per year). In the 94 women, (35%) with a history of previous non-vertebral fractures, ultrasound parameters were significantly lower (p < 0.0001) than in the 176 women with no history of fracture (-8.3% for BUA, -1.3% for SOS, -18.9% for stiffness index). In contrast, there was no significant difference in anthropometric measurements between the groups with and without previous non-vertebral fractures, although the measurements decreased significantly with age. In the longitudinal study, repeated quantitative ultrasound after 11.4 +/- 0.8 months showed no significant decrease in BUA (-1%) but a significant decrease in SOS (-0.3%, p < 0.0001) and in stiffness index (-3.6%, p < 0.0002). In conclusion, quantitative ultrasound of the calcaneus measures properties of bone which continue to decline in institutionalized elderly women, and is able to discriminate women with previous non-vertebral fractures.

Aged↗
PubMed1996

Bone densitometry of the forearm: comparison of single-photon and dual-energy X-ray absorptiometry.

Forearm bone mineral densitometry was performed initially by single-photon absorptiometry (SPA), but is now achievable by dual-energy X-ray absorptiometry (DXA) as well, with a good correlation between both measurements. However, it is still unknown whether: (1) short-term precision of DXA is superior to SPA and (2) identical regions of interest (ROI) are mandatory to correlate SPA with DXA. The aim of this study was to answer these questions using a commercial system for DXA (DXA-FAS) and to test an in-house system using spine DXA and a soft-tissue compensator (DXA-STC). In ten subjects, four measurements on the same day showed significantly lower (p < 0.05) coefficients of variation (CV) for bone mineral density (BMD) by DXA-FAS (proximal site: 0.74%; ultradistal site: 1.20%) than by SPA (1.26% and 2.25%). However, the CV for bone mineral content (BMC) were similar for DXA-FAS (0.73% and 1.58%) and SPA (0.79% and 1.34%). The significant difference (p < 0.05) for surface calculation by DXA-FAS (1.24% and 0.93%) compared with SPA (2.36% and 1.28%) explains all the advantages of DXA-FAS for short-term precision. The measurements taken on the same day on the ulna and the radius or on the radius alone by SPA, DXA-FAS, and DXA-STC on 108 subjects aged 18-80 years were highly correlated [r ranging from 0.925 to 0.995 (p < 0.0001) and standard error of the estimate from 3.15% to 8.89%]. The need for a manual adjustment of the ROI was found to be mandatory for BMC but not BMD assessment. The use of DXA-STC is a fast method for forearm bone densitometry and its correlation with SPA is very high. However, its short-term precision for BMC (3.00% and 1.54%), BMD (2.15% and 1.12%), and surfaces (1.99% and 1.12%) is significantly higher (p < 0.05) than that of DXA-FAS. We conclude that short-term precision of DXA is better than that of SPA only for BMD and surface measurement but not for BMC. ROI should be adjusted manually for the assessment of BMC but not for that of BMD.

Absorptiometry, Photon↗
PubMed1996

Cyclosporine induces high bone turnover and may contribute to bone loss after heart transplantation.

Cardiac transplantation has become a successful therapy for end-stage heart disease. However, increased bone loss has been observed in heart transplant recipients, sometimes being responsible for osteoporotic fractures. Glucocorticoids cause dose-related bone loss, particularly in the first 6-12 months of use, but cyclosporine might play a role as well. The evolution of bone mineral density (BMD) and biochemical parameters was prospectively assessed in 24 patients (mean age 52 years) from cardiac transplantation. All patients received cyclosporin A (CsA) and prednisone, the latter at decreasing dosage. The mean current daily dose of CsA was 321 mg and serum levels of CsA were constant. All patients received calcium (500 mg day-1) and vitamin D (1000 U day-1) for prevention of bone loss. BMD (gcm-2) was measured in 17 patients at the lumbar spine, femoral neck and total hip with dual energy X-ray absorptiometry every 6 months. Spinal BMD as well as neck and total hip BMD decreased at 6 and 12 months after transplantation, being statistically significant at the three sites: -5.6 and -3.4% for the lumbar spine, -9.3 and -8.5% for the femoral neck, -4.8% and -6.0% for the total hip respectively. Parathyroid hormone (PTH) and osteocalcin (BGP) increased by 90% and 800% respectively between pretransplantation values and 18 months after transplantation. BGP levels measured every 2 months from transplantation increased continuously from 8.7 micrograms L-1 (mean +/- SEM) before transplantation to 31.3 +/- 10.1 (P < 0.05) at 4 months, to 59.1 +/- 8.8 (P < 0.01) at 6 months and to 72.2 +/- 9.9 (P < 0.01) at 18 months (Kruskal-Wallis analysis: P < 0.0001). PTH showed a biphasic pattern with an initial decrease from 39.3 +/- 4.1 ng L-1 at baseline to 22.0 +/- 2.8 ng L-1 at 2 months, but increasing thereafter to 45.9 +/- 5.7 at 6 months and 74.2 +/- 8.9 at 18 months (Kruskal-Wallis analysis: P < 0.001). These variations represent a glucocorticoid-induced osteoporosis. In summary, cardiac transplant patients lose bone immediately after transplantation at the spine and the hip. Later on, the loss in BMD discontinues at all sites of the skeleton, but predominantly at the spine, and a few patients still lose bone at the hip. This is probably a result of the high bone turnover either due to secondary hyperparathyroidism or induced by cyclosporin A.

Adult↗
PubMed1996

Bone mineral content in cystic fibrosis patients: correlation with fat-free mass.

OBJECTIVE: To assess the bone mineral content in well nourished patients with cystic fibrosis and to seek a correlation with fat-free mass. METHODS: Fourteen cystic fibrosis patients aged 6 to 20 years were studied and compared to 14 healthy controls matched for gender, age, and nutritional status. Bone mineral content was determined by dual energy x ray absorptiometry (DEXA). RESULTS: Nutritional inquiry showed higher ingestion of macronutrients and micronutrients by cystic fibrosis patients than by controls. Mean whole skeleton bone mineral content was 1.184 (SD 0.536) kg in cystic fibrosis patients and 1.229 (0.576) kg in controls (p = 0.84). Mean lumbar spine bone mineral content was 0.031 (0.013) kg and 0.031 (0.016) kg, respectively (p = 0.99). Anthropometry, bioelectrical impedance analysis, and DEXA showed that fat-free mass was similar in the two groups. Bone mineral content was strongly correlated to fat-free mass. Mean blood calcium, phosphorus, serum 25-hydroxyvitamin D (25-OHD), parathyroid hormone (PTH), and osteocalcin were similar in both groups. CONCLUSIONS: Bone mineral content and body composition are normal in a well nourished young cystic fibrosis population. Osteopenia previously reported in cystic fibrosis patients probably has nutritional origins and is therefore not related to a primary defect in bone mineral metabolism.

Adolescent↗