Strontium ranelate: dose-dependent effects in established postmenopausal vertebral osteoporosis--a 2-year randomized placebo controlled trial.

The aim of the strontium ranelate (SR) for treatment of osteoporosis (STRATOS) trial was to investigate the efficacy and safety of different doses of SR, a novel agent in the treatment of postmenopausal osteoporosis. A randomized, multicenter, double-blind, placebo-controlled trial was undertaken in 353 osteoporotic women with at least one previous vertebral fracture and a lumbar T-score <-2.4. Patients were randomized to receive placebo, 0.5 g, 1 g, or 2 g SR/d for 2 yr. The primary efficacy endpoint was lumbar bone mineral density (BMD), assessed by dual-energy x-ray absorptiometry. Secondary outcome measures included femoral BMD, incidence of new vertebral deformities, and biochemical markers of bone metabolism. Lumbar BMD, adjusted for bone strontium content, increased in a dose-dependent manner in the intention-to-treat population: mean annual slope increased from 1.4% with 0.5 g/d SR to 3.0% with 2 g/d SR, which was significantly higher than placebo (P < 0.01). There was a significant reduction in the number of patients experiencing new vertebral deformities in the second year of treatment with 2 g/d SR [relative risk 0.56; 95% confidence interval (0.35; 0.89)]. In the 2 g/d group, there was a significant increase in serum levels of bone alkaline phosphatase, whereas urinary excretion of cross-linked N-telopeptide, a marker of bone resorption, was lower with SR than with placebo. All tested doses were well tolerated; the 2 g/d dose was considered to offer the best combination of efficacy and safety. In conclusion, SR therapy increased vertebral BMD and reduced the incidence of vertebral fractures.

Comparison of four morphometric definitions and a semiquantitative consensus reading for assessing prevalent vertebral fractures.

The assessment of vertebral fracture in patients with osteoporosis by conventional radiography has been improved over the past 10 years using either the semiquantitative (SQ) method devised by Genant et al. or quantitative morphometry. However, there is still no internationally agreed definition for vertebral fracture and there have been few comparative studies between these different approaches. Our study assessed the reproducibility of the SQ method and of four commonly used morphometric algorithms (Melton's, Eastell's, Minne's and McCloskey's methods) for assessing prevalent vertebral fractures, and examined the agreement of each morphometric algorithm with a SQ consensus reading performed by three experts. With this consensus reading in place of a gold standard, we determined relative measures of sensitivity, specificity and optimal cutoff threshold for each morphometric algorithm. The study was conducted in 39 postmenopausal women who had at least one osteoporotic vertebral fracture. Normal values were derived from 84 healthy postmenopausal women with apparently normal vertebral bodies. Our results indicate that the concordance of SQ method was excellent (intraobserver agreement on serial radiographs = 96.4%, kappa = 0.91; agreement between individual readings and the consensus reading = 98%, kappa = 0.95). Three morphometric approaches demonstrated good intra- and interobserver concordance (Melton: intraobserver agreement on serial radiographs = 92.7%, kappa = 0.82, interobserver agreement = 91.1%, kappa = 0.79; Eastell: intraobserver agreement on serial radiographs = 87.6%, kappa = 0.66, interobserver agreement = 88.6%, kappa = 0.68; McCloskey: intraobserver agreement on serial radiographs = 91.5%, kappa = 0.72, interobserver agreement = 93.9%, kappa = 0.78). Except for McCloskey's method, the optimal cutoff thresholds defined in our study by highest kappa score or Youden index in comparison with the SQ consensus reading were near the cutoff thresholds that were arbitrarily fixed. The four morphometric algorithms provided a good agreement with the results of the SQ consensus reading, but the more complex algorithm did not provide better results and even if we adjusted the cutoff threshold, no morphometric algorithm agreed perfectly with the SQ consensus reading. We conclude that morphometric approaches currently used should not be employed alone to detect prevalent vertebral fractures in studies on osteoporosis, but should rather be used in combination with a visual assessment. The SQ approach that allows differential diagnosis of vertebral deformities and has demonstrated a better reproducibility can be employed alone when it is performed by experienced and well-trained readers.

Forceful sacrococcygeal injections in the treatment of postdiscectomy sciatica. A controlled study versus glucocorticoid injections.

UNLABELLED: The role of epidural fibrosis in postoperative sciatica is unclear. Few therapeutic trials have been published. We evaluated the mechanical effects of forceful saline injections through the sacrococcygeal hiatus comparatively with glucocorticoid injections. PATIENTS AND METHODS: Forty-seven patients with postdiscectomy sciatica but no evidence of compression by computed tomography or magnetic resonance imaging were included in a multicenter, randomized, controlled, parallel-group study comparing forceful injections of saline (20 ml) with or without prednisolone acetate (125 mg) to epidural prednisolone acetate (125 mg) alone. Each of the three treatments was given once a month for three consecutive months. Outcome measures were pain severity on a visual analog scale (VAS) and the scores on the Dallas algofunctional self-questionnaire on day 0, day 60, and day 120. Analysis of variance for repeated measures and Student's t test for paired series were used to evaluate the data. RESULTS: Forty-seven patients were evaluated. The VAS score improved significantly between day 0 and day 30 in the glucocorticoid group as compared to the forceful injection group (P = 0.01). No other significant differences were found across the groups. The VAS score improved steadily in the forceful injection group, producing a nearly significant difference on day 120 as compared to baseline (P = 0.08). CONCLUSION: Forceful epidural injections produced a non-significant improvement in postdiscectomy sciatica four months after surgery. Epidural glucocorticoids used alone induced short-lived pain relief.

Influence of age and sex on vertebral shape indices assessed by radiographic morphometry.

Vertebral shape indices (VSI) assessed by radiographic morphometry are currently used to define vertebral fractures in clinical trials and epidemiologic studies on osteoporosis. However, there is little information concerning the influence of sex or age on VSI. Furthermore, previous reports on the variation of VSI with age showed conflicting results. The aim of this study was to assess the influence of sex and age on VSI in order to better define reference values for the clinical and epidemiologic evaluation of vertebral osteoporotic fractures. Measurements were performed on thoracic and lumbar spine radiographs from 50 men and 50 women (age range 25-75 years) without evidence of osteoporotic, degenerative or other disease-related vertebral deformity. The anterior (AH), middle (MH) and posterior (PH) heights of each vertebral body from T4 to L5 were measured and VSI were calculated as follows: wedging = (AH minus PH) divided by PH; concavity = (MH minus PH) divided by PH. Wedging and concavity, especially at the mid and lower thoracic spine, increased significantly with age in both sexes. We also demonstrated that VSI at the lumbar spine were significantly dependent on gender, with greater values of wedging and concavity in men than in women. Consequently, reference values used for the definition of vertebral osteoporotic fractures assessed by radiographic morphometry should take into account both sex and age effects.

The use of different dual X-ray absorptiometry brands in a multicenter clinical trial: consequences and limits.

Accurate cross-calibration (CC) and quality control (QC) programs for dual X-ray absorptiometry (DXA) instruments are necessary in order to guarantee appropriate measurements of bone mineral density (BMD) during longitudinal studies. This article details the CC-QC program established for the STRATOS study, a multicenter clinical trial investigating the effects of strontium ranelate on osteoporotic women with vertebral fractures. Forty-five DXA instruments of different brands (namely, 27 Hologic, 9 Lunar, 5 Norland, and 4 Sopha) were cross-calibrated at the beginning of the study. Twenty-seven of these were still in use by the end of the study. The CC was performed at the beginning and at the end of the study by measuring a unique spine phantom 20 times. The in vitro reproducibility of measurements. (coefficient of variation [CV]) was calculated from the results of the phantom measurements. The in vivo CV was obtained from pairs of measurements of the lumbar spine and the hip of the patients at the time of inclusion in the study. Initial in vitro CV averaged 0.5%. At the end of the study, the CC performed for the 27 apparatus in use at the end of the trial provided long-term intrabrand in vitro CV of 0.7% for the Hologic (n = 18), 1% for the Lunar (n = 5), and 0.3% for the Norland (n = 4) DXA instruments. The in vivo short-term CV for the lumbar spine BMD measurements was suboptimal, as opposed to the hip measurements, and was most likely due to the age of the population investigated. The results of measurements of multibrand DXA apparatus in this multicenter study suggest several practical conclusions: (1) the CC should be performed by using a single phantom independent of the DXA brand tested; (2) duplicate measurements should be performed at the time of patient inclusion; (3) the most efficient QC program should include CC, central reading of in vivo scans, and central review of daily QC.

How hip and whole-body bone mineral density predict hip fracture in elderly women: the EPIDOS Prospective Study.

We conducted a population-based cohort study in 7598 white healthy women, aged 75 years and over, recruited from the voting lists. We measured at baseline bone mineral density (BMD g/cm2) of the proximal femur (neck, trochanter and Ward's triangle) and the whole body, as well as fat and lean body mass, by dual-energy X-ray absorptiometry (DXA). One hundred and fifty-four women underwent a hip fracture during an average 2 years follow-up. Each standard deviation decrease in BMD increased the risk of hip fracture adjusted for age, weight and centre by 1.9 (95% CL 1.5, 2.3) for the femoral neck, 2.6 times (2.0, 3.3) for the trochanter, 1.8 times (1.4, 2.2) for Ward's triangle, 1.6 times (1.2, 2.0) for the whole body, and 1.3 times (1.0, 1.5) for the fat mass. The areas under the receiver operating characteristic (ROC) curves were not significantly different between trochanter and femoral neck BMD, whereas ROC curves of femoral neck and trochanter BMD were significantly better than those for Ward's triangle and whole-body BMD. Women who sustained an intertrochanteric fracture were older (84 +/- 4.5 years) than women who had a cervical fracture (81 +/- 4.5 years) and trochanter BMD seemed to be a stronger predictor of intertrochanteric ([RR = 4.5 (3.1, 6.5)] than cervical fractures ([RR = 1.8 (1.5, 2.3]). In very elderly women aged 80 years and more, hip BMD was still a significant predictor of hip fracture but the relative risk was significantly lower than in women younger than 80 years. In the 48% of women who had a femoral neck BMD T-score less than -2.5, the relative risk of hip fracture was increased by 3, and the unadjusted incidence of hip fracture was 16.4 per 1000 woman-years compared with 1.1 in the population with a femoral neck BMD T-score > or = -1.

[Long-term stability of bone mineral density in patients with renal transplant treated with cyclosporine and low doses of corticoids. Protective role of cyclosporine?]. / Stabilité à long terme de la densité minérale osseuse des transplantés rénaux sous ciclosporine et faibles doses de corticoïdes. Rôle protecteur de la ciclosporine?

OBJECTIVES: Cyclosporine has been thought to have a deleterious effect on bone in transplant recipients because of high turnover osteopenia observed in humans after transplantation. However, varying confounding factors such as renal and parathyroid function, cumulative steroid doses and previous exposure to aluminium, also play a role and hinder interpretation of the cyclosporine effect on bone mineral density (BMD). PATIENTS AND METHODS: A 2-year prospective study was conducted to measure BMD starting 3 months after transplantation and bone remodeling markers from the first post-transplantation day in 52 kidney recipients with no prior exposure to aluminum. None of the patients experienced rejection and at 3 months all had good stable renal function (serum creatinine 137 mumol/l) and mildly elevated parathyroid hormone levels (1.5 times the upper limit of normal). All patients were given the same low dose steroid treatment (10 mg/day) and at 6 months cyclosporine was decreased from 7 to 4.8 mg/kg/day. RESULTS: BMD measured by double energy X-ray absorptiometry, (DEXA) and expressed in Z score, was moderately decreased at 3 months for the vertebrae (-1.40), the femoral neck (-1.34) and the ultradistal radius (-0.95) which have predominantly cancellous bone and was significantly less decreased (p < 0.05) for the lower third of the radius (-0.6) which is mainly cortical bone. BMD measurements were comparable at 6, 12 and 24 months. When measured by axial computerized tomography (ACT) BMD of the vertebrae showed a non-significant increase of Z score from -1.37 to -1.19 at 2 years. Bone remodeling markers was observed up to month 6 (from month 3 for osteocalcine and from month 1 for total and bone alkaline phosphatase and urinary pyridinoline), then returned to baseline levels at 2 years in parallel with decreased cyclosporine dosage. The increase of vertebral BMD measured by ACT at 1 year was correlated both to cyclosporine dose at 1 year and to bone alkaline phosphatase at 6 months. CONCLUSION: Our data confirm the presence of moderate osteopenia 3 months after transplantation, predominantly in trabecular bone, logically linked to the initial high doses of corticosteroids. The long-term stability of BMD measured by DEXA and the correlation of vertebral BMD increase measured by ACT with cyclosporine dose and bone alkaline phosphate suggest that cyclosporine had a beneficial immunosuppressor effect by stimulating bone remodeling and thus counterbalancing the suppressive effect of corticosteroids.

Fluoride salts are no better at preventing new vertebral fractures than calcium-vitamin D in postmenopausal osteoporosis: the FAVOStudy.

Although fluoride salts have been shown to be capable of linearly increasing spinal bone mineral density (BMD) in postmenopausal osteoporosis, the effects of this gain in density on the vertebral fracture rate remain controversial. We conducted a 2-year multicenter, prospective, randomized, double-masked clinical trial in 354 osteoporotic women with vertebral fractures (mean age 65.7 years). They received either fluoride (208 patients), given as sodium fluoride (50 mg/day) or as monofluorophosphate (200 mg/day or 150 mg/day), or a placebo (146 patients). All patients received daily supplements of 1 g of calcium (Ca) and 800 IU of vitamin D2 (D). A 1-year open follow-up on Ca-D was obtained in 124 patients. After 2 years the fluoride group and the Ca-D group had increased their lumbar BMD by 10.8% and 2.4% respectively (p = 0.0001). However, the rate of patients with at least one new vertebral fracture, defined by semiquantitative assessment and evaluable on an intention-to-treat basis in 89% of patients, was similar in the fluoride groups and the Ca-D group. No difference between the three fluoride regimens was found. The percentage of patients with nonvertebral fractures was not different in the fluoride and Ca-D groups (1.9% and 1.4% respectively for hip fractures). A lower limb pain syndrome occurred more frequently in the fluoride groups. In the 124 patients followed for 1 year after cessation of fluoride therapy, the percentage of patients with at least one new vertebral fracture after 36 months was identical to the percentages in the previous fluoride group and the Ca-D group. We conclude that fluoride-Ca-D regimen was no more effective that Ca-D supplements for the prevention of new vertebral fractures in women with postmenopausal osteoporosis.

Response of several markers of bone collagen degradation to calcium supplementation in postmenopausal women with low calcium intake.

We investigated the response of bone-specific resorption markers in fasting urine samples from postmenopausal women with low daily dietary calcium (Ca) intake (<800 mg/day) who received either Ca supplementation (1200 mg/day, n = 18) or placebo (n = 14) for 2 months. We measured urinary hydroxyproline, total pyridinoline, and deoxypyridinoline by HPLC, and free deoxypyridinoline (i-F-Dpd) and N- and C-telopeptide fragments of type I collagen (NTX and CTX) by immunoassays. Before supplementation, the urine concentrations of bone resorption markers in the 32 subjects were not statistically different from those measured in 21 subjects with daily dietary Ca intake >800 mg/day. In contrast to the placebo group, Ca supplementation decreased all collagen-related degradation markers except i-F-Dpd as early as the first month. The magnitude of response after 2 months of Ca supplementation, expressed as mean percentage of decrease from baseline values or as individual Z scores, was greatest for the telopeptide assays. Furthermore, the percentage of change assessed at 2 months was greater than the within-person biological variability (CV) assessed in the placebo-treated women for NTX and CTX, whereas for the other markers the percentage of change was very close of the within-person CVs. We conclude that cross-linked telopeptide fragments of type I collagen most sensitively reflect the change in bone resorption after Ca supplementation.

Biochemical effects of calcium supplementation in postmenopausal women: influence of dietary calcium intake.

We studied the biochemical effects of calcium supplementation during a 2-mo course in postmenopausal women (x +/- SD: 64 +/- 5 y of age and 14.5 +/- 6.7 y since menopause). The effects on calcium homeostasis and bone remodeling were assessed after 1 and 2 mo of daily administration of either calcium carbonate (1200 mg elemental Ca/d, n = 60) or a placebo (n = 56). The daily dietary calcium intake assessed before the beginning of calcium supplementation was 786 mg/d. We found a significant inverse relation between baseline intact parathyroid hormone (iPTH) and dietary calcium intake before supplementation (r = -0.48, P = 0.0002). A significant increase in urinary excretion of pyridinoline was observed when the dietary calcium intake was lower than the median value. Calcium supplementation resulted in a significant increase in 24-h urinary calcium (39%, P < 0.02) and a significant reduction of bone alkaline phosphatase at 2 mo and of all bone-resorption markers (hydroxyproline, pyridinoline, and deoxypyridinoline) at I and 2 mo without significant changes in 44-68 PTH fragments or iPTH concentrations. When the dietary calcium intake was low (mean +/- SD: 576 +/- 142 mg/d), calcium supplementation was responsible for a greater increase in urinary calcium excretion and a greater decrease in markers of bone turnover. The greatest variations were observed for deoxypyridinoline at 1 and 2 mo (-18.5%, P < 0.05) and for pyridinoline at 1 mo (-16.3%, P < 0.01). Two months of calcium supplementation in postmenopausal women was efficient in reducing markers of bone turnover, with a greater effect in women with a low dietary calcium intake.

Two new cancer locations accompanied with palmar fasciitis and polyarthritis.

Only 35 cases of cancer with palmar fasciitis and polyarthritis have been published to date. We report two new cases, one with a transitional cell carcinoma of the renal pelvis and the other with an adenocarcinoma of the uterus. Neither of these locations has been reported in association with palmar fasciitis and polyarthritis. Palmar fasciitis with polyarthritis can occur in a wide range of cancers and warrants extensive investigations for a malignant tumor.

Broadband ultrasound attenuation at the calcaneus measured using a new contact ultrasound unit.

We evaluated a new contact ultrasound device, developed and manufactured in France, for measuring broadband ultrasound attenuation at the calcaneus. We first studied the influence on measurement results of a number of parameters including the nature of the coupling agent, heel position, transducer temperature, and foot vasodilation. We then determined the reproducibility of the measurements (2.14 +/- 1.07% in the medium-term) and established reference values in women (n = 612) and men (n = 106). Broadband ultrasound attenuation decreased between 25 and 85 years of age by 34% in women and 17% in men. Sensitivity and specificity for detection of decreased bone mass at the calcaneus were 85.5% and 81.5%, respectively. Sensitivity and specificity of the measurement at the calcaneus as compared to the lumbar spine were 90.7% and 89.1%, respectively. This unit intended for screening purposes is very easy to use, and the measurements it provides are immediately available. It can be expected to help determine the optimal strategy for use of ultrasound in the management of osteoporosis.

An epidemiological study of diagnostic and therapeutic strategies in office practice patients with subacute or chronic pain in the thoracic or low back. Comparison of practices in primary care and rheumatology settings.

UNLABELLED: There is a paucity of epidemiological data on diagnostic and therapeutic practices in office practice patients with subacute or chronic pain in the thoracic or low back. STUDY OBJECTIVE: to describe diagnostic and therapeutic strategies used in such patients. PATIENTS AND METHODS: descriptive, prospective, two-month epidemiological study in 50 general practitioners and 50 rheumatologists. Each physician was asked to provide data on the demographics, clinical features, history of spinal disease, investigations, prior treatments and treatments prescribed on D0 and D30 in two patients with low back pain and two with thoracic back pain, of one to 12 months' duration. RESULTS: A total of 352 patients were included. In the 217 patients with low back pain, including 107 women and 110 men, duration of the pain was 4.3 +/- 0.2 months and mean age was 49.6 +/- 1 years; 67% of these patients were economically active and 22% were retired; 59% were recruited by rheumatologists. In the thoracic back pain group, there were 135 patients, including 82 women (61%) and 53 men, with a mean duration of pain of 3.8 +/- 0.3 months and a mean age of 47.7 +/- 1.4 years; 60% were economically active and 22% were retired; 49% were recruited by rheumatologists. A history of conservatively-treated low or thoracic back pain was reported for 95.4% of patients in the low back pain group and 94% in the thoracic back pain group. Of the patients with low back pain, 6.3% had had spinal surgery. Investigations were as follows: roentgenograms in 85% of low back pain and 75% of thoracic back pain patients, computed tomography in 11% and 5.8%, magnetic resonance imaging in 2% and 1% and laboratory tests in 14% and 20%. Ninety-one per cent of low back pain and 84% of thoracic back pain patients were already under therapy on D0. Ninety-six per cent of patients overall were given a prescription at the end of the D0 visit, for a nonsteroidal antiinflammatory drug or an analgesic in 80% of low back pain and 63% of thoracic back pain patients, for muscle relaxants in 62% and 69%, for drugs aimed at preventing gastric side effects in 19% and 9.5%, for myotonic agents in 10% and 8% and for sedatives in 5% and 11%. A local steroid injection was given to 20% of low back pain patients. Twenty-four per cent of low back pain and 14% of thoracic back pain patients missed days of work (mean, 11 +/- 1.7 days and 13 +/- 4.6 days, respectively). Physical therapy was prescribed to 36% of low back pain and 27% of thoracic back pain patients and a lumbar support belt to 17% of low back pain patients. On D30, the pain had abated in 86% of low back pain and 89% of thoracic back pain patients and complete freedom from pain was reported by 28% and 32% of patients in these two groups, respectively. Treatments prescribed on D30 were physical therapy (43% and 31%), analgesics (40% and 36%) muscle relaxants (25% and 30%), and nonsteroidal antiinflammatory drugs (23% and 12%). Conclusion. This preliminary study provides data on common practices in subacute and chronic low back and back pain and may prove useful for health care cost estimations.

Effects of cyclical etidronate therapy on bone loss in early postmenopausal women who are not undergoing hormonal replacement therapy.

This study was carried out to investigate the effectiveness and tolerability of cyclical etidronate therapy in the prevention of bone loss occurring in early postmenopausal women who are not undergoing hormone replacement therapy (HRT). A total of 109 Caucasian women aged 45-60 years were treated with etidronate 400 mg/day or placebo for 14 days followed by calcium supplementation 500 mg/day for 77 days. Ninety-one women completed the 2 years of the study. After 2 years, the estimated difference between the two groups as regards lumbar spine bone mineral density (BMD) was 2.53% (SEM 1.07%; p = 0.01); BMD of the hip and wrist were not significantly different between treatment groups. A clear reduction in bone turnover was obtained as evidenced by a significant decrease in serum alkaline phosphatase level and in urinary N-telopeptide/ creatinine ratio in the etidronate group; the difference between the two groups was -12% +/- 3.2% for serum alkaline phosphatase level (p = 0.019) and -22.9% +/- 13.7% for the urinary N-telopeptide/creatinine ratio (p = 0.047). There was no statistically significant difference between the two groups in terms of the serum osteocalcin levels and urinary hydroxyproline/ creatinine and calcium/creatinine ratios. Etidronate was generally well tolerated and its adverse event profile was similar to that of placebo. The results of this study indicate that cyclic etidronate therapy can prevent trabecular bone loss, with no deleterious effect on cortical bone, in the first 5 years of menopause and that it has a very high safety margin.

Fluoride therapy for bone disease.

The use of fluoride in the treatment of osteoporosis remains very controversial, despite its registration in many countries. Fluoride has been convincingly demonstrated to have a potent anabolic effect on osteoblastic trabecular bone formation, with a subsequent sustained increase in axial bone mass. However, its ability to reduce the vertebral fracture rate in established spinal osteoporosis is still debated, and questions have been raised regarding a potential negative effect on cortical bone mass and an increase in fractures of the peripheral skeleton, especially hip fractures. These data, including some very recent studies, are reviewed to draw some perspectives and recommendations for the use of fluoride in the treatment of osteoporosis.

Different responses of free and peptide-bound cross-links to vitamin D and calcium supplementation in elderly women with vitamin D insufficiency.

Recent findings have shown that bisphosphonates had different effects on the urinary excretion of free and peptide-bound cross-links. Because of this discrepancy, we investigated the effects of another antiresorptive therapy, i.e. vitamin D (vitD) and calcium (Ca) supplementation (800 IU vit D3 and 1 g elemental calcium daily for 6 months) in elderly women (n = 21, age: 83.5 +/- 1.5 yr) with vitD insufficiency and secondary hyperparathyroidism (mean level 25 hydroxy vitamin D = 3.17 +/- 1.2 ng/mL, mean level of intact parathormone = 45.3 +/- 22.7 pg/mL) on the urinary excretion of free and peptide-bound cross-links. A group of free-living, healthy elderly women (n = 25, age: 76.6 +/- 3.1 yr) with a normal vitD status (mean level of 25 OH D = 23.4 +/- 8.9 ng/mL, intact parathormone = 30.2 +/- 11.2 pg/mL) was simultaneously studied. Bone resorption was assessed by total (T), free (F), peptidyl (P) hydroxylysylpyridinoline (HP) and lysylpyridinoline (LP) measured with high performance liquid chromatography, by F-LP determined with enzyme linked immunosorbent assay (iF-LP) and by the N- and C-terminal telopeptides of type I collagen (NTX and Cross-laps) before and after (3 and 6 months) therapy. Comparison of the two groups of elderly women at baseline showed that the urinary excretion of pyridinoline cross-links (T, F, and peptide-bound forms) and of telopeptide fragment of type I collagen were all increased in patients with a low vitD status. Highly significant differences were seen principally for T-HP, F-HP, and F-LP (P < 0.001). Correlation studies between each marker showed that the values of pyridinoline cross-links (T and peptide-bound forms) and of the telopeptide fragments of type I collagen correlated well, but the correlation was slightly less pronounced between free pyridinolines and the other markers. After treatment, the response to therapy was greatest for peptide-bound cross-links assessed by high performance liquid chromatography and for telopeptide fragments of type I collagen (percent change at 6 months: -21% for P-HP P < 0.05, -26% for P-LP P < 0.05, -31% for NTX P < 0.01, and -51% for CLaps P < 0.001). In contrast, free pyridinolines excretion (F-HP and F-LP) assessed by high performance liquid chromatography as well as by immunoassay remained unchanged at 3 and 6 months. Because marked and significant changes were seen with peptide-bound cross-links only and not with free forms, we conclude that vitD and Ca therapy has the same effects as bisphosphonates on the urinary excretion of free and peptide-bound cross-links. So far, no rational mechanism can be given to explain this discrepancy, and further studies are needed before routine application of these bone collagen degradation products as bone resorption markers.

Ultrasonographic heel measurements to predict hip fracture in elderly women: the EPIDOS prospective study.

BACKGROUND: The ability of ultrasonographic measurements to discriminate between patients with hip fracture and age-matched controls has until now been tested mainly through cross-sectional studies. We report the results of a prospective study to assess the value of measurements with ultrasound in predicting the risk of hip fracture. METHODS: 5662 elderly women (mean age 80.4 years) had both baseline calcaneal ultrasonography measurements and femoral radiography (dual-photon X-ray absorptiometry, DPXA) to assess their bone quality. Follow-up every 4 months enabled us to identify incident fractures. 115 hip fractures were recorded during a mean follow-up duration of 2 years. FINDINGS: Low calcaneal ultrasonographic variables (obtained from measurements of broadband ultrasound attenuation by, and speed of sound through the bone) were able to predict an increased risk of hip fracture, with similar accuracy to low femoral bone mineral density (BMD) obtained by DPXA. The relative risk of hip fracture for 1 SD reduction was 2.0 (95% CI 1.6-2.4) for ultrasound attenuation and 1.7 (1.4-2.1) for speed of sound, compared with 1.9 (1.6-2.4) for BMD. After control for the femoral neck BMD, ultrasonographic variables remained predictive of hip fracture. The incidence of hip fracture among women with values above the median for both calcaneal ultrasound attenuation and femoral neck BMD was 2.7 per 1000 woman-years, compared with 19.6 per 1000 woman-years for those with values below the median for both measures. INTERPRETATION: Ultrasonographic measurements of the os calcis predict the risk of hip fracture in elderly women living at home as well as DPXA of the hip does, and the combination of both methods makes possible the identification of women at very high or very low risk of fracture.