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Biomedical subjects

J C Roos

Publications and source records attributed to J C Roos.

At least 19 recordsLinked to original sources

Additional weight bearing during exercise and estrogen in the rat: the effect on bone mass, turnover, and structure.

Mechanical loading and estrogen play important roles in bone homeostasis. The aim of this study was to evaluate the effects of mechanical loading on trabecular bone in the proximal femur of ovariectomized rats. We hypothesized that mechanical loading suppresses bone resorption and increases bone formation, which differs from the suppressive effects of estrogen on both resorption and formation. Furthermore, we expected to find changes in trabecular architecture elicited by the effects of mechanical loading and estrogen deficiency. Sixty female Wistar rats, 12 weeks old, were assigned to either the sedentary groups sham surgery (SED), ovariectomy (SED+OVX), and ovariectomy with estrogen replacement (SED+OVX+E2) or to the exercise groups EX, EX+OVX, EX+OVX+E2. Following ovariectomy, 5 microg 17beta-estradiol was given once weekly to the estrogen replacement groups. Exercise consisted of running with a backpack (load +/-20% of body weight) for 15 minutes/day, 5 days/week, for 19 weeks. Dual-energy X-ray absorptiometry (DXA) scans were performed before (T0), during (T6), and after (T19) the exercise period to obtain bone mineral content (BMC) and bone mineral density (BMD) data. After the exercise program, all rats were killed and right and left femora were dissected and prepared for micro-CT scanning and histomorphometric analysis of the proximal femoral metaphysis. After 19 weeks, increases in BMC (P = 0.010) and BMD (P = 0.031) were significant. At T19, mechanical loading had a significant effect on BMC (P = 0.025) and BMD (P = 0.010), and an interaction between mechanical loading and estrogen (P = 0.023) was observed. Bone volume and trabecular number decreased significantly after ovariectomy, while trabecular separation, mineralizing surface, bone formation rate, osteoclast surface, degree of anisotropy, and structure model index increased significantly after ovariectomy (P < 0.05). Trabecular bone turnover and structural parameters in the proximal femur were not affected by exercise. Estrogen deficiency resulted in a less dense and more oriented trabecular bone structure with increased marrow cavity and a decreased number of trabeculae. In conclusion, mechanical loading has beneficial effects on BMC and BMD of the ovariectomized rat. This indicates that the load in the backpack was high enough to elicit an osteogenic response sufficient to compensate for the ovariectomy-induced bone loss. The results confirm that estrogen suppresses both bone resorption and bone formation in the proximal metaphysis in the femoral head of our rat-with-backpack model. The effects of mechanical loading on the trabecular bone of the femoral head were not significant. This study suggests that the effect of mechanical loading in the rat-with-backpack model mainly occurs at cortical bone sites.

Absorptiometry, Photon↗

Imaging and serum analysis of immune complex formation of radiolabelled infliximab and anti-infliximab in responders and non-responders to therapy for rheumatoid arthritis.

BACKGROUND: Many patients with rheumatoid arthritis are currently successfully treated with infliximab (anti-tumour necrosis factor); however, about 30% of the patients do not respond to infliximab. One of the postulated hypotheses of not responding is the fast clearance of infliximab due to the development of infliximab-anti-infliximab complexes. OBJECTIVE: To investigate the in vivo mechanism of not responding and the role of human anti-chimeric antibodies (HACAs) by using radiolabelled infliximab. METHODS: Two responding and two non-responding patients with rheumatoid arthritis, infused with radiolabelled infliximab, were investigated by both imaging and serum analysis. RESULTS: Images showed predominant presence of infliximab in blood up to 24 h, with a trend of faster blood clearance and of higher liver/spleen uptake in a non-responding patient. Clinically inflamed joints showed uptake of the drug. The HACA level in the non-responders was high (1641 and 1008 U/ml), but low or not detectable in responders. Sucrose gradients of serum showed antibody complexes in both non-responders. Various sizes of antibody complexes, including very large ones, were observed in a non-responder who developed a serious infusion reaction. CONCLUSION: Formation of infliximab-anti-infliximab complexes were found in non-responders due to the presence of large amounts of HACA. This finding, supported by both imaging and serum analysis data, may explain failure of infliximab treatment.

Adult↗

Reproducibility of bone mineral density measurement in daily practice.

BACKGROUND: Bone mineral density (BMD) measurements are frequently performed repeatedly for each patient. Subsequent BMD measurements allow reproducibility to be assessed. OBJECTIVE: To examine the reproducibility of BMD by dual energy x ray absorptiometry (DXA) and to investigate the practical value of different measures of reproducibility in a group of postmenopausal women. METHODS: Ninety five women, mean age 59.9 years, underwent two subsequent BMD measurements of spine and hip. Reproducibility was expressed as smallest detectable difference (SDD), coefficient of variation (CV), and intraclass correlation coefficient (ICC). Sources of variation were investigated by multilevel analysis. RESULTS: The median interval between measurements was 0 days (range 0-45). The mean difference (SD) between the measurements (g/cm(2)) was -0.001 (0.02) and -0.0004 (0.02) at L1-4 and the total hip, respectively. At L1-4 and the total hip, SDD (g/cm(2)) was +/-0.05 and +/-0.04 and CV (%) was 1.92 and 1.59, respectively. The ICC at spine and hip was 0.99. CONCLUSIONS: Reproducibility in the postmenopausal women studied was good. In a repeated DXA scan a BMD change exceeding 2 radical 2CV (%), the least significant change (LSC), or the SDD should be regarded as significant. Use of the SDD is preferable to use of the CV and LSC (%) because of its independence from BMD and its expression in absolute units. Expressed as SDD, a BMD change of at least +/-0.05 g/cm(2) at L1-4 and +/-0.04 g/cm(2) at the total hip should be considered significant.

Absorptiometry, Photon↗

[Iodine prophylaxis to prevent radiation damage following nuclear disasters].

After the Twin Tower attack on 11 September 2001, much attention is being given to possible terrorist attacks on nuclear targets. However, most of this interest is in countries outside of the Netherlands. Iodine is a simple and effective means of preventing part of the radiation damage following a nuclear disaster. Non-radioactive (stable) iodine plays an important part in blocking the absorption of radioactive iodine by the thyroid gland, if it is administered as soon as possible after the nuclear accident has occurred. Prophylaxis with 100 mg non-radioactive iodide has a minimal toxic effect. Effective iodine prophylaxis is dependent on the government ensuring a well-regulated distribution. The government and hospitals should have thorough protocols that staff are sufficiently familiar with.

Humans↗

Radioimmunodiagnosis of lymph node metastases in head and neck cancer.

INTRODUCTION: Reliable staging of the neck remains a diagnostic challenge in head and neck squamous cell carcinoma (HNSCC) patients. Monoclonal antibodies (MAbs) directed against tumour-associated antigens can be used for selective tumour targeting. When labelled with a gamma-emitting radionuclide like 99mTechnetium, such MAbs can be used for tumour detection by radioimmunoscintigraphy (RIS). OBJECTIVE: The aim of this study was to assess the potential of RIS for the detection of lymph node metastases in HNSCC patients. PATIENTS AND METHODS: In 49 patients with HNSCC, who were scheduled to undergo surgery including neck dissection, RIS using 99mTc-labelled squamous cell specific MAb E48 or U36 administered intravenously was compared with clinical palpation, computed tomography (CT), magnetic resonance imaging (MRI) and histopathological outcome. RESULTS: RIS detected lymph node metastases in 35 of 51 positive sides (sensitivity 69%). Interpretation of RIS was correct in 47 of 65 sides (accuracy 72%). Accuracy of palpation, CT and MRI were comparable. Immunohistochemical staining of lymph node metastases missed by RIS showed that the injected MAb had targeted these small tumour deposits but these were not visualized. CONCLUSIONS: RIS at its current stage of development is not superior to CT or MRI for the detection of lymph node metastases. As small tumour deposits were probably not visualized because of the limited sensitivity and/or spatial resolution of the gamma camera, positron emission tomography (PET) using MAbs labelled with positron emitters may improve the detection. As MAb-PET studies in an animal model showed promising results we will soon start a clinical MAb-PET study.

Antibodies, Neoplasm↗

[Comparable case finding percentages of osteoporosis despite diverging reasons for ordering bone densitometry by general practitioners and specialists].

OBJECTIVE: To assess the use of bone densitometry in practice. DESIGN: Retrospective. METHOD: General practitioners who had ordered bone densitometry for their patients were asked to fill in a questionnaire on the reasons for the request and the subsequent treatment they prescribed. For a similar number of patients from the outpatient clinics of general internal medicine and endocrinology, the medical records were examined to obtain the same information. RESULTS: In 9 months, general practitioners requested 150 bone density measurements; for 117 of these the data were complete. In one year, 150 measurements were requested by the outpatient clinics. Marked differences in the reasons for the request were seen in loss of body height, back pain and requests from the patient (indications for general practitioners) and in osteoporotic fractures and the use of corticosteroids (indications for specialists). The average result of the measurements, however, was the same, with mean T-scores in the lumbar spine of -2.26 and -2.19, respectively and case-finding percentages of osteoporosis of 21% on the basis of the lumbar spine and 40% on the basis of the spine or hip. Bone densitometry carried out after an osteoporotic fracture was associated with the lowest mean bone mineral density, followed by measurement on the basis of abnormal X-rays. Bone densitometry at the patient's request was associated with the highest bone density. The percentage of patients found to have osteoporosis turned out to be dependent on the site of measurement, the used reference ranges, and the method of reporting, especially for patients older than 70 years. When the bone density corresponded to a diagnosis of osteoporosis, nearly all patients were treated, mainly with a bisphosphonate. Treatment was also frequently started when the bone density was reduced, i.e. in case of osteopenia. Some patients with normal bone density were treated as well. The reason for such treatment was not always clear. CONCLUSION: General practitioners and specialists used different risk factors in deciding whether bone densitometry was indicated. However, the two groups used this diagnostic tool with equal efficiency, since both the percentages of osteoporosis detected and the average bone densities were the same.

Absorptiometry, Photon↗

Effect of 1 year of discontinuation of raloxifene or estrogen therapy on bone mineral density after 5 years of treatment in healthy postmenopausal women.

The beneficial effects of hormone replacement therapy (HRT), selective estrogen receptor modulators (SERMs), or bisphosphonates in the prevention and treatment of osteoporosis in postmenopausal women have been well established. However, little is known about the effects of discontinuation of treatment on bone mineral density. We investigated the effect of 1 year of discontinuation of the SERM raloxifene (Ral; 60 mg and 150 mg), conjugated equine estrogen (CEE; 0.625 mg), and placebo after 5 years of treatment in a double-blind, randomized study. Thirty-eight of 59 healthy and hysterectomized postmenopausal women (mean age 55 years) completed the treatment and 1 year follow-up period. Lumbar spine and femoral neck bone mineral density (BMD) were performed with dual-energy X-ray absorptiometry, before, during, and at the end of treatment, as well as after 1 year of discontinuation of therapy. One year of discontinuation significantly reduced the mean lumbar spine BMD in the raloxifene- and estrogen-treated women (p < 0.05), whereas mean femoral neck BMD was reduced significantly only in women treated with 60 mg Ral (p < 0.05). The mean percentage change (+/-SD) in lumbar spine BMD was: CEE, -6.2% (+/-3.7%); Ral 60 mg, -2.4% (+/-2.4%); Ral 150 mg, -2.6% (+/-3.1%); and placebo, -1.6% (+/-4.3%). Our results show that 5 years of treatment with either Ral or CEE did not protect against bone loss after 1 year of withdrawal of therapy, and that the rate of bone loss was not significantly different from that of placebo-treated women.

Bone Density↗

Bone metabolism markers and bone mass in healthy pubertal boys and girls.

OBJECTIVE: During puberty, bone growth and mineralization as well as bone turnover increase dramatically. The relation between height velocity and bone turnover is already known, but there are few studies in which both bone metabolism markers and bone mass throughout puberty have been measured. DESIGN: Semi-longitudinal study. In 155 healthy boys (12.0 +/- 1.5 years; range 8.8-15.7 years) and 151 healthy girls (11.2 +/- 1.6 years; range 8.2-14.0 years) markers of bone formation and bone resorption were measured as well as sex steroids, IGF-1 and IGF-BP3, together with bone mineral content (BMC) and bone mineral density (BMD) of the lumbar spine, femur and total body during puberty. All bone measurements were repeated after 1 year. RESULTS: BMC and BMD increased throughout puberty in both sexes. Bone turnover markers increased significantly until maximum values were reached at stage G4 in boys and stage B3 in girls. Height velocity (HV) had a similar changing pattern. Sex steroids and IGF-1 increased and reached adult values at pubertal stage 4. The correlations between bone metabolism markers and BMC were highly significant in boys, while correlations between bone metabolism markers and the increase in BMC over 1 year were significant in both sexes, as was observed for the correlations with HV. CONCLUSIONS: Our data suggest that bone metabolism markers are good predictors of bone mass in boys and of bone mass increase in both sexes. In early puberty, sex steroids stimulate the pubertal growth spurt in conjunction with GH and IGF-1. The fast increase in height gives rise to an increase in bone turnover and bone mineral apposition. It is known that at the end of puberty high levels of oestradiol inhibit chondrocyte proliferation. This leads to a decline in height velocity and bone turnover. Bone mass still increases under the influence of sex steroids and IGF-1. The data in our study confirm previous reports that markers of bone turnover relate positively to height velocity.

Adolescent↗

Body composition in infants with chronic lung disease after treatment with dexamethasone.

UNLABELLED: The aim of this study was to study the effect of chronic lung disease (CLD) and dexamethasone treatment on body composition in preterm infants (birthweight < 1500 g). In addition, anthropometric measurement of body composition were compared with dual-energy X-ray absorptiometry (DXA). Fourteen preterm infants with CLD and a comparison group of 18 preterm infants were studied until 3 mo corrected age. CLD infants received approximately 20 kcal kg-1 per day extra nutritional intake during dexamethasone treatment until term. At term no differences were found between CLD and no CLD infants for percentage bone mass (1.4 +/- 0.2 vs 1.4 +/- 0.1%), fat mass (18.7 +/- 4.5 vs 17.4 +/- 3.5%), lean body mass (79.9 +/- 4.6 vs 81.2 +/- 3.5%) or bone mineral density (0.15 +/- 0.02 vs 0.15 +/- 0.01%). At 3 mo corrected age both groups were also similar for bone mass (1.6 +/- 0.1 vs 1.6 +/- 0.2%), fat mass (22.6 +/- 5.5 vs 24.5 +/- 5.7%), lean body mass (75.8 +/- 5.7 vs 74.0 +/- 5.8%) and bone mineral density (0.20 +/- 0.02 vs 0.20 +/- 0.01%). All anthropometric measurements showed a high correlation with body composition. However, calculated fat mass was 56.7 +/- 8.8% lower than fat mass measured with DXA. CONCLUSION: Body composition at term and 3 mo corrected age in preterm infants treated with dexamethasone for CLD, who received extra caloric intake until term, did not differ from that in preterm infants without CLD.

Absorptiometry, Photon↗

Alendronate in the prevention of bone loss after a fracture of the lower leg.

Fracture of a leg and the consequent absence from weight-bearing lead to local bone loss. A 1-year, single-center, prospective, randomized, double-blind study was conducted, to determine whether bone loss would occur in the proximal femur and the calcaneus after a fracture of the lower leg and whether this loss could be prevented by the antiresorptive drug bisphosphonate alendronate. Twenty-three men and 18 women with a recent unstable fracture of the lower leg were randomized to receive either 10 mg of alendronate daily or placebo. Bone mineral density (BMD) of both hips and the lumbar spine was measured at baseline and 6 weeks and 3, 6, and 12 months after start of the treatment. Quantitative ultrasound (QUS) measurements of the calcaneus were performed at baseline on the noninjured side and at 6 weeks and 3, 6, and 12 months after start of treatment on both sides. After 1 year, in the placebo group, there was a significant decrease from baseline in BMD of the hip on the side of the fracture. In the alendronate group, there was no significant change from baseline. The differences in BMD between the two treatment groups on the side of the fracture were significant in all sites of the hip: 4.4% (p = 0.016) in the trochanter, 4.6% (p = 0.016) in the femoral neck, and 3.9% (p = 0.009) in the total hip. In the hip on the contralateral side, there were no significant changes from baseline in either treatment group and there was no difference between the two treatment groups. BMD in the lumbar spine increased in the alendronate group, and after 1 year there was a significant difference between the active treatment and placebo group of 3.4% (p = 0.04). One year after fracture, ultrasound parameters of the calcaneus in the placebo group were significantly lower on the fractured side compared with the contralateral side (p < 0.01). In the alendronate group, no significant difference between the two sides was observed. In conclusion, BMD of the proximal femur was still decreased 1 year after a fracture of the lower leg. Alendronate prevented this bone loss.

Adult↗

Influence of the route of administration on targeting of ovarian cancer with the chimeric monoclonal antibody MOv18: i.v. vs. i.p.

MOv18 antibody binds the membrane folate receptor highly expressed on ovarian carcinoma cells. Since ovarian cancer is mainly limited to the peritoneal cavity, locoregional delivery of therapeutics can be an option. The same patient was injected i.v. and i.p. with c-MOv18 IgG labeled with different radionuclides. To study the kinetics of c-MOv18, patients were divided into 2 groups. Fifteen patients received c-MOv18 labeled with (131)I, (125)I and (123)I (for imaging). Seven patients were operated 2 days, 7 patients 6 days and 1 patient 3 days post-injection. Radioactivity was determined in blood, ascites and biopsies of tumor and of several normal tissues. No adverse events occurred. No anti-MOv18 responses were observed. The area under the blood activity vs. time curve (AUC) was significantly lower after i.p. injection for 2 and 6 days post-injection (p = 0.01 and p = 0.02, respectively). At 2 days post-injection, a significant difference in tumor uptake was found in favor of the i.v. route of administration (4.9% and 2.4%ID/kg for i.v. and i.p., respectively; p < 0.0001). Uptake in solid tumor tissue in ovarian cancer patients operated 6 days post-injection was not significantly different (p = 0.79) for both routes (3.8% and 3.9%ID/kg for i.v. and i.p., respectively). In conclusion, no advantage could be demonstrated for the i.p. route with respect to tumor uptake. The i.p. route could be advantageous with respect to bone marrow toxicity since the AUC was significantly lower for the i.p. route. However, within 2 days post-injection, the blood clearance followed the same pattern for both routes.

Adult↗

Radioimmunotherapy in patients with head and neck squamous cell carcinoma: initial experience.

BACKGROUND: Despite improvements in locoregional treatment of stages III/IV squamous cell carcinoma of the head and neck (HNSCC), local and distant failure rates remain high. An effective adjuvant therapy is required for these patients. Among novel approaches is radioimmunotherapy, in which monoclonal antibodies (MAbs) are used for selective delivery of radiation to tumor cells. METHODS: The suitability of 186Re-labeled chimeric MAb U36 (186Re-cMAb U36) for radioimmunotherapy was evaluated in a phase I study, with radiation dose escalating steps of 11, 27, and 41 mCi/m2. Tumor targeting was monitored with a gamma camera, and the maximum tolerated dose was established in 13 patients with recurrent or metastatic disease. RESULTS: Administrations were well tolerated, and excellent targeting of tumor lesions was seen. Myelotoxicity was the only toxicity observed, resulting in dose-limiting toxicity in two patients treated with 41 mCi/m2. The MTD was established at 27 mCi/m2. A marked reduction in tumor size was observed in two patients, another showed stable disease for 6 months. CONCLUSIONS: Radioimmunotherapy with 186Re-cMAb U36 seems to be well tolerated, with bone marrow being the dose-limiting organ. The observation of antitumor effects is encouraging for further development of radioimmunotherapy for HNSCC.

Aged↗

Detection of osteomyelitis using FDG and positron emission tomography.

A positron emission tomography (PET) scan with 2-[fluorine-18]fluoro-2-deoxy-D-glucose ((18)FDG) was performed on a patient with clinical and laboratory signs of infection after a removed hip prosthesis but with indistinct signs on the bone scan and radiographs. The PET scan confirmed the clinical and laboratory signs and revealed an unidentified focus of infection in the distal area of the right femur.

Adult↗

Determinants of bone mineral density in older men and women: body composition as mediator.

This study aimed to assess the relative importance of several determinants of bone mineral density (BMD) and to examine to what extent these potential determinants influence total hip BMD through body composition. The study population consisted of 522 participants (264 women and 258 men) of the Longitudinal Aging Study Amsterdam (LASA), aged 65 years and over, and living in Amsterdam and its vicinity. BMD of the total hip was measured using dual-energy X-ray absorptiometry (DXA). Potential determinants of BMD were age, weight change since age 25 years, lifestyle factors, chronic diseases, medication use, and hormonal factors. Potential mediators between the possible determinants and BMD were two measures of body composition: fat mass (FM) and appendicular muscle mass (AMM). Multiple regression analyses including all potential determinants in one model without body composition identified age, weight change, walking activity, and sex hormone-binding globulin (SHBG) as independent determinants for total hip BMD in women. In men, current smoking, participation in sports, and parathyroid hormone (PTH) concentration were independently associated with total hip BMD. When total hip BMD was regressed on the potential determinants and each measure of body composition, it appeared that FM, and to a lesser extent, muscle mass (MM), were independently related to BMD. In women, adjustment for FM reduced the strength of the associations of weight change, walking activity, and SHBG with total hip BMD. Adjustments for MM did not influence the associations between the determinants and BMD. In men, neither FM nor MM appeared to play a mediating role between the determinants and BMD. It can be concluded that (1) FM and MM are strong independent determinants of total hip BMD and that (2) FM possibly plays a mediating role in the association of weight change, walking activity, and SHBG with total hip BMD in women.

Adipose Tissue↗

Pubertal maturation characteristics and the rate of bone mass development longitudinally toward menarche.

To assess risks for osteoporosis and to compare bone mass in different groups of healthy children or children with diseases, it is important to have knowledge of their sexual maturation status during puberty. The aim of our study was to evaluate bone mass formation longitudinally in relation to pubertal maturation characteristics in healthy white girls. We investigated the bone mineral content (BMC) and the bone mineral density (BMD) at different skeletal sites in 151 girls with increasing pubertal stages in relation with their chronological age and with an early or late onset of puberty or menarche and with a slow or fast maturation. Bone mass was measured at the onset of puberty, during puberty, and at menarche. We conclude the following: (1) from midpuberty to menarche, the increase in bone mass formation is highest at all skeletal sites in white girls; (2) early mature girls at the onset of puberty have slightly but definitely lower bone masses at all skeletal sites and at all pubertal stages than late mature girls, whereas the average bone mass formation from the onset of puberty to menarche is similar in both groups; (3) girls with a slow rate of pubertal maturation have lower bone mass values 2 years after the onset of puberty, but at menarche bone mass is similar compared with fast maturers; and (4) it cannot be confirmed that there is an effect of menarcheal age on bone mass values at menarche.

Absorptiometry, Photon↗

Evaluation of limited blood sampling in a preceding 99mTc-labeled diagnostic study to predict the pharmacokinetics and myelotoxicity of 186Re-cMAb U36 radioimmunotherapy.

UNLABELLED: 186Re-labeled chimeric monoclonal antibody U36 (cMAb U36) was recently evaluated in a phase I dose escalation study in head and neck cancer patients. All 13 patients received 99mTc-labeled cMAb U36 before 186Re-cMAb U36 radioimmunotherapy. The aim of this study was to evaluate the suitability of multiple or limited blood sampling to predict clearance, red marrow absorbed dose, and myelotoxicity of 186Re-cMAb U36. METHODS: Population pharmacokinetics of 186Re-cMAb U36 were analyzed with a nonparametric expectation algorithm (NPEM 2) and used for Bayesian analysis of individual patient data to predict cMAb U36 clearance. RESULTS: 186Re-cMAb U36 clearance was most accurately predicted (r = 0.91, P < 0.001) with limited sampling for sample points 4 and 72 h after administration of 186Re-cMAb U36. These predictions were less accurate with 99mTc-cMAb U36 (r = 0.51, P = 0.078 for multiple sampling; r = 0.47, P = 0.104 for sampling at 4 and 21 h after administration). Thrombocytopenia was found to be correlated with the red marrow absorbed dose and was equally well predicted by limited blood sampling after administration of 99mTc-cMAb U36 (r = 0.81, P < 0.01) or 186Re-cMAb U36 (r = 0.79, P < 0.01). CONCLUSION: Limited sampling seems useful to predict pharmacokinetics and myelotoxicity of 186Re-cMAb U36.

Aged↗

Predictors of fractures in elderly women.

In a prospective study of 348 apparently healthy women, aged 70 years and over (mean 80.3 years), we examined bone mineral density (BMD), biochemical markers of bone metabolism, and some easily measurable predictors in relation to hip and osteoporotic fractures. In addition, we constructed risk profiles for hip and osteoporotic fractures. At baseline, BMD at both hips, using dual-energy X-ray absorptiometry, body height and body weight were measured. At the same time, serum and urine samples were obtained for biochemical analysis. Serum samples were analyzed for vitamin D metabolites, sex hormone binding globulin, serum intact parathyroid hormone, osteocalcin, alkaline phosphatase, phosphate, albumin, calcium and creatinine. In 2 h fasting urine, hydroxyproline, type I collagen crosslinked N-telopeptide (NTx) and calcium excretion were measured. Furthermore, easily measurable predictors, such as previous fracture, body mass index (BMI) and mobility were assessed. During the follow-up period (mean duration 5.0 years), hip and any osteoporotic fracture (wrist, humerus or hip fracture) occurred in 16 and 33 participants, respectively. Data were analyzed using Cox regression analysis. BMD of the trochanter (per 1 SD decrease) and previous fracture were most strongly associated with hip fractures (adjusted relative risk (RR) = 3.0, 95% confidence interval (CI): 1.4-6.6; RR = 4.2, 95% CI: 1.5-11.6, respectively) and osteoporotic fractures (RR = 1.8, 95% CI: 1.1-2.8; RR = 2.9, 95% CI: 1.5-5.7, respectively). Previous fracture, BMI and mobility were identified as easily measurable predictors for hip fractures, whereas previous fracture, use of loop diuretics and age were predictors for osteoporotic fractures in the risk profile model. The risk of fractures can be predicted with three easily measurable predictors. This study confirms the importance of previous fracture as a predictor for hip fractures and other fractures. It also shows that the use of loop diuretics is a predictor for osteoporotic fractures.

Activities of Daily Living↗