The ties of ILAR and WHO.
Explore the source record for details and available documents.
Education, Medical, Undergraduate↗
Biomedical subjects
J Dequeker
Publications and source records attributed to J Dequeker.
Recombinant human interleukin-11 does not modify biochemical parameters of bone remodeling and bone mineral density in adult ovariectomized rats.
Interleukin (IL)-11 stimulates osteoclast formation and inhibits osteoblast function in vitro and has been implicated in estrogen deficiency-induced bone loss. Herein we report the in vivo effect of recombinant human IL-11 (rHU-IL-11), administered s.c. in doses between 10 and 200 microg/kg/day for 6 weeks into 6-month-old rats after ovariectomy. There was no difference between vehicle-treated and rHu-IL-11 treated rats in the ovariectomy-induced increase in the urinary excretion of pyridinoline and deoxypyridinoline. Neither was there a significant effect of rHu-IL-11 on the plasma concentrations of osteocalcin and on bone mineral density (BMD) measured at a metaphyseal area of the distal femur after 6 weeks. At all dosages tested, rHu-IL-11 increased the femoral diaphyseal area. In conclusion, IL-11 has no deleterious in vivo effect on biochemical parameters of bone remodeling and BMD in estrogen-deficient rats.
Amino Acids↗
Gastrointestinal tolerability of meloxicam compared to diclofenac in osteoarthritis patients. International MELISSA Study Group. Meloxicam Large-scale International Study Safety Assessment.
Although widely used, non-steroidal anti-inflammatory drugs (NSAIDs) are associated with a high incidence of gastrointestinal (GI) side-effects. Inhibition of the cyclooxygenase (COX) enzyme is the basis for both the efficacy and toxicity of NSAIDs. The discovery of two COX isoforms, constitutive COX-1 and inducible COX-2, has led to the hypothesis that selective inhibition of COX-2 will minimize the potential for GI toxicity without compromising efficacy. The Meloxicam Large-scale International Study Safety Assessment (MELISSA) trial reported here was therefore set up to investigate the tolerability of meloxicam, a preferential inhibitor of COX-2, compared to diclofenac. MELISSA was a large-scale, double-blind, randomized, international, prospective trial, conducted over 28 days in patients with symptomatic osteoarthritis. Patients received either meloxicam 7.5 mg or diclofenac 100 mg slow release, the recommended doses for the treatment of osteoarthritis. Evaluation of the profile of adverse events was the main aim of the trial, together with assessment of efficacy. A total of 9323 patients received treatment (4635 and 4688 in the meloxicam and diclofenac groups, respectively). Significantly fewer adverse events were reported by patients receiving meloxicam. This was attributable to fewer GI adverse events (13%) compared to diclofenac (19%; P < 0.001). Of the most common GI adverse events, there was significantly less dyspepsia (P < 0.001), nausea and vomiting (P < 0.05), abdominal pain (P < 0.001) and diarrhoea (P < 0.001) with meloxicam compared to diclofenac. Five patients on meloxicam experienced a perforation, ulcer or bleed vs seven on diclofenac (not significant). No endoscopically verified ulcer complication was detected in the meloxicam group compared to four with diclofenac. There were five patient days of hospitalization in patients on meloxicam compared to 121 with diclofenac. Adverse events caused withdrawal from the study in 254 patients receiving meloxicam (5.48%) compared to 373 (7.96%) on diclofenac (P < 0.001). These differences were attributable to differences in reported GI adverse events (3.02% on meloxicam vs 6.14% on diclofenac; P < 0.001). Differences in efficacy, as assessed by visual analogue scales, consistently favoured diclofenac. In all instances, 95% confidence intervals did not cross zero, suggesting a statistically significant effect. However, differences were small (4.5-9.01% difference) and did not reach pre-determined levels of clinical significance. Nevertheless, significantly more patients discontinued meloxicam because of lack of efficacy (80 out of 4635 vs 49 out of 4688; P < 0.01). The MELISSA trial confirms earlier studies suggesting that meloxicam has a significantly improved GI tolerability profile in comparison with other NSAIDs, including diclofenac. These results may in part reflect the preferential COX-2 selectivity of meloxicam, although the dose and other aspects of tolerability may be important. These results may provide support for the hypothesis that selective inhibition of COX-2 relative to COX-1 might be an effective approach towards improved NSAID therapy.
Aged↗
Improvement in gastrointestinal tolerability of the selective cyclooxygenase (COX)-2 inhibitor, meloxicam, compared with piroxicam: results of the Safety and Efficacy Large-scale Evaluation of COX-inhibiting Therapies (SELECT) trial in osteoarthritis.
SELECT is a large-scale, prospective, international, multicentre, double-blind, double-dummy, randomized, parallel-group trial. Patients with exacerbation of osteoarthritis were treated with the recommended dose of meloxicam (7.5 mg) or piroxicam (20 mg) once daily for 28 days; 4320 patients were administered meloxicam and 4336 piroxicam. The incidence of adverse events was significantly lower in the meloxicam group (22.5%) compared with the piroxicam group (27.9%; P < 0.001), mainly due to the significantly lower incidence of gastrointestinal (GI) adverse events in the meloxicam than in the piroxicam group (10.3% vs 15.4%,; P < 0.001), while the efficacy of both drugs was equivalent. Individual GI events occurred significantly less often with meloxicam than piroxicam: dyspepsia (3.4% vs 5.8%; P < 0.001), nausea/vomiting (2.5% vs 3.4%; P < 0.05) and abdominal pain (2.1% vs 3.6%; P < 0.001). There were 16 patients with perforations, ulcerations or bleeding (PUBs) of the upper GI tract in the piroxicam group compared with seven in the meloxicam group (relative risk piroxicam:meloxicam = 1.4). Four PUBs were complicated (perforations or bleedings); none of these occurred in the meloxicam group (relative risk piroxicam:meloxicam = 1.9). The outcome of SELECT is consistent with that of the large-scale clinical trial of similar design and size which compared 7.5 mg meloxicam with 100 mg diclofenac in patients with osteoarthritis, and with a previous global analysis of the safety of meloxicam. It adds further data to the proposed relationship between selective inhibition of cyclooxygenase-2 and improved GI tolerability of non-steroidal anti-inflammatory drugs.
Aged↗
Cyclical etidronate increases bone density in the spine and hip of postmenopausal women receiving long term corticosteroid treatment. A double blind, randomised placebo controlled study.
OBJECTIVE: To study the effect of cyclic etidronate in secondary prevention of corticosteroid induced osteoporosis. METHODS: A double blind, randomised placebo controlled study comparing cyclic etidronate and placebo during two years in 37 postmenopausal women receiving long term corticosteroid treatment, mainly for polymyalgia rheumatica (40% of the patients) and rheumatoid arthritis (30%). Bone density was measured in the lumbar spine, femoral neck, and femoral trochanter. RESULTS: After two years of treatment there was a significant difference between the groups in mean per cent change from baseline in bone density in the spine in favour of etidronate (p = 0.003). The estimated treatment difference (mean (SD)) was 9.3 (2.1)%. Etidronate increased bone density in the spine (4.9 (2.1)%, p < 0.05) whereas the placebo group lost bone (-2.4 (1.6)%). At the femoral neck there was an estimated difference of 5.3 (2.6)% between the groups (etidronate: 3.6% (1.4)%, p < 0.05, placebo: -2.4 (2.1)%). The estimated difference at the trochanter was 8.2 (3.0) (etidronate: 9.0 (1.5)%, p < 0.0001, placebo: 0.5 (2.3)%). No significant bone loss occurred in the hip in placebo treated patients. CONCLUSIONS: Cyclic etidronate is an effective treatment for postmenopausal women receiving corticosteroid treatment and is well tolerated.
Aged↗
Interspecies differences in bone composition, density, and quality: potential implications for in vivo bone research.
This study compares bone composition, density, and quality in bone samples derived from seven vertebrates that are commonly used in bone research: human, dog, pig, cow, sheep, chicken, and rat. Cortical femoral bone samples were analyzed for their content of ash, collagen, extractable proteins, and insulin-like growth factor-I. These parameters were also measured in bone powder fractions that were obtained after separation of bone particles according to their density. Large interspecies differences were observed in all analyses. Of all species included in the biochemical analyses, rat bone was most different, whereas canine bone best resembled human bone. In addition, bone density and mechanical testing analyses were performed on cylindrical trabecular bone cores. Both analyses demonstrated large interspecies variations. The lowest bone density and fracture stress values were found in the human samples; porcine and canine bone best resembled these samples. The relative contribution of bone density to bone mechanical competence was largely species-dependent. Together, the data reported here suggest that interspecies differences are likely to be found in other clinical and experimental bone parameters and should therefore be considered when choosing an appropriate animal model for bone research.
Adult↗
Distraction bone healing versus osteotomy healing: a comparative biochemical analysis.
This study investigates the biochemical changes in a canine tibia lengthening model in comparison with a nonlengthened osteotomy model. The lengthened and the osteotomized callus and a contralateral corresponding segment were analyzed for their mineralization profile, collagen content, osteocalcin, insulin-like growth factor I (IGF-I), and transforming growth factor beta1 (TGF-beta1). Examinations of bone samples were performed using specimens excised at different time intervals (respectively at 3, 5, 7, 9, and 13 weeks postoperatively). Several serum parameters (alkaline phosphatase [ALP], osteocalcin, IGF-I, and TGF-beta1) were also measured during the experimental period. A progressive increase in mineral parameters was noticed in both the lengthened and the osteotomized areas. A higher level of hydroxyproline and TGF-beta1 was observed in the lengthened area compared with the osteotomized area. IGF-I showed a significant increase in both the lengthened and contralateral control area at the later stage of the experimental period in the lengthened group. In serum, a high level of TGF-beta1 and a progressively increasing osteocalcin concentration were observed in the lengthened dogs in comparison with the osteotomized dogs. Serum ALP was significantly increased in both models during the experimental period. Serum IGF-I was increased in the lengthened models during the distraction period and decreased in the osteotomized models at the early stage of the experimental period. These results suggest that the mechanical strain induced by the Ilizarov distraction procedure stimulates osteoblast proliferation and promotes biosynthesis of bone extracellular matrix in distracted callus. Our data furthermore show that this process is different compared with normal fracture healing.
Alkaline Phosphatase↗
Prediction of vertebral and femoral strength in vitro by bone mineral density measured at different skeletal sites.
The aim of the present study was to investigate the prediction of vertebral and femoral strength in vitro by bone mineral density (BMD) measured at different skeletal sites. The third lumbar vertebral body, the right proximal femur, and the right calcaneus were removed from 38 male and 32 female cadavers (mean age 69 years, range 23-92 years). Areal BMD of all bone specimens was determined by dual-energy X-ray absorptiometry (DXA). The failure load of the vertebral body and the femur was determined by mechanical testing. Vertebral and femoral strength were both greater in males than females (p < 0.01), as was BMD at all sites (p < 0.01). Vertebral strength correlated well with vertebral BMD (r2 = 0.64) but was only moderately correlated with BMD measured at the femur (r2 = 0.36) or the calcaneus (r2 = 0.18). Femoral strength showed the highest correlations with femoral BMD (r2 = 0.88) and somewhat weaker relationships with BMD at the vertebra (r2 = 0.50) and the calcaneus (r2 = 0.54). BMD values at the vertebra, femur, and calcaneus were only moderately interrelated (r2 = 0.31-0.65), and vertebral strength correlated only modestly with the strength of the femur (r2 = 0.36). These in vitro results support the concept that optimal prediction of vertebral or femoral strength by DXA requires site-specific assessments.
Absorptiometry, Photon↗
High prevalence and impact of rheumatic diseases is not reflected in the medical curriculum: the ILAR Undergraduate Medical Education in Rheumatology (UMER) 2000 project. Together everybody achieves more. International League of Associations for Rheumatology.
Explore the source record for details and available documents.
Aged↗
Bone density and local growth factors in generalized osteoarthritis.
Osteoarthritis is usually considered to be a primary disorder of chondrocyte function with secondary changes in bones. However, a defect in the subchondral bone resulting in loss of its shock absorbing capacity could transfer the stress of loading directly to the articular cartilage with secondary changes in the cartilage. Review of histomorphometric and bone densitometric studies at sites of osteoarthritis at the hip or knee revealed that cartilage fibrillation could not be dissociated from bony changes even in the earliest stages of osteoarthritis and that subchondral trabeculae are thickened and more spaced in osteoarthritis. Microfractures of subchondral trabecular bone were less frequently seen in osteoarthritis compared to controls. Changes of the tidemark were found to be multiform and metabolically active in the osteoarthritic process. Endochondral ossification depletes the calcified cartilage at the cartilage/bone interface and the tidemark has been thought of as a calcification front advancing in the direction of non-calcified cartilage. Duplication of the tidemark is cited as evidence of this advancement. In the few experimental animal studies of subchondral bone in osteoarthritis, thicker trabeculae which were closer together were found in guinea pigs already when only mild cartilage changes were present. In the dog, with cruciate ligament transection, changes in bone were later than in the cartilage, but the changes in bone could still contribute to the progression of osteoarthritis. To study if bone changes may precede injury to the cartilage and if metabolic and systemic influences can also alter the subchondral bone, rendering it less able to withstand normal mechanical stresses, bone at different sites in the body has been studied extensively by the authors. Epidemiological and case control studies have revealed that osteoarthritis cases have more bone at all sites than expected and that bone in cases with generalized osteoarthritis shows both quantitative and qualitative differences, including increased contents of growth factors and hypermineralization. These findings suggest that a more generalized bone alteration may be the basis of the pathogenesis of osteoarthritis.
Animals↗
Total lymphoid irradiation in rheumatoid arthritis. A ten-year followup.
OBJECTIVE: To report the findings of a 10-year followup of patients enrolled in a randomized trial of total lymphoid irradiation (TLI) versus chemotherapy for rheumatoid arthritis (RA). METHODS: A retrospective analysis of the charts of 19 patients who had been included in a randomized trial comparing TLI and chemotherapy for the treatment of RA. RESULTS: Ten years after the start of the trial, a higher number of TLI-treated patients had died (7 of 10), compared with patients who had received chemotherapy (2 of 9). In addition, 3 of the TLI-treated patients developed B cell-related malignancies, whereas no such malignancies developed in the control group. CONCLUSION: TLI was associated with a less-favorable long-term outcome than chemotherapy. These data stress the importance of careful long-term followup in experimental trials of immunosuppressive agents.
Aged↗
Clonal expansion of mycobacterial heat-shock protein-reactive T lymphocytes in the synovial fluid and blood of rheumatoid arthritis patients.
OBJECTIVE: To examine the reactivity pattern and T cell receptor (TCR) characteristics of mycobacterial heat-shock protein 65 (hsp65)-reactive T cells generated from paired synovial fluid (SF) and peripheral blood (PB) samples obtained from rheumatoid arthritis (RA) patients and from healthy subjects. METHODS: The reactivity pattern of hsp65-reactive T cell clones generated under limiting-dilution conditions was analyzed in 3H-thymidine incorporation assays. The TCR variable regions of these hsp65-reactive T cells were characterized by polymerase chain reaction with TCR AV- and BV-specific primers and by DNA sequence analysis of the third complementarity-determining region (CDR3). RESULTS: The hsp65-reactive T cells derived both from RA patients and controls preferentially recognized the 1-170 and 303-540 regions of hsp65 and did not cross-react with human hsp60. The hsp65-reactive T cell clones derived from RA patients displayed a restricted TCR AV and BV gene usage, which can be attributed to the limited clonal origin(s) of the independent T cell clones, as evidenced by CDR3 sequence analysis. These clonally expanded T cells were found in both PB and SF and in different inflamed joints of RA patients. CONCLUSION: Our study suggests that there is in vivo clonal activation and expansion of mycobacterial hsp65-reactive T cells in patients with RA.
Antigens, Bacterial↗
Biochemical and density assessment of the new bone in late remodeling after callus distraction.
Biochemical changes in a canine bone-lengthening model were characterized 5 months after surgery. The mineral content and the total amount of EDTA-extractable noncollagenous proteins, insulin-like growth factor-I, and osteocalcin were determined for the lengthened callus, and a gradient density fractionation analysis of bone powder particles was performed. The results were compared with two other areas of the lengthened tibia and one region of the contralateral tibia. The mineral and osteocalcin contents showed significant decreases, whereas the hydroxyproline concentration was significantly increased. Neither the insulin-like growth factor-I content nor the concentration of EDTA-extractable proteins was significantly different in any of the examined regions.
Animals↗
Population-based geographic variations in DXA bone density in Europe: the EVOS Study. European Vertebral Osteoporosis.
The purpose of this study was to investigate variations in bone density between 16 European populations, 13 of which were participants in the European Vertebral Osteoporosis Study (EVOS). Men and women aged 50-80 years were recruited randomly from local population registers, stratified in 5-year age bands. The other three centres recruited similarly. Random samples of 20-100% of EVOS subjects were invited for dual-energy X-ray absorptiometry (DXA) densitometry of the lumbar spine and/or proximal femur using Hologic, Lunar or Norland pencil beam machines or, in one centre, a Sopha fan-beam machine. Cross-calibration of the different machines was undertaken using the European Spine Phantom prototype (ESPp). Highly significant differences in mean bone density were demonstrated between centres, giving rise to between centre SDs in bone density that were about a quarter of a population SD. These differences persisted when centres using Hologic machines and centres using Lunar machines were considered separately. The centres were ranked differently according to whether male or female subjects were being considered and according to site of measurement (L2-4, femoral neck or femoral trochanter). As expected, bone mineral density (BMD) had a curvilinear relationship with age, and apparent rates of decrease slowed as age advanced past 50 years in both sexes. In the spine, not only did male BMD usually appear to increase with age, but there was a highly significant difference between centres in the age effect in both sexes, suggesting a variability in the impact of osteoarthritis between centres. Weight was consistently positively associated with BMD, but the effects of height and armspan were less consistent. Logarithmic transformation was needed to normalize the regressions of BMD on the independent variates, and after transformation, all sites except the femoral neck in females showed significant increases in SD with age. Interestingly, the effect of increasing weight was to decrease dispersion in proximal femur measurements in both sexes, further accentuating the tendency in women for low body mass index to be associated with osteoporosis as defined by densitometry. It is concluded that there are major differences between BMD values in European population samples which, with variations in anthropometric variables, have the potential to contribute substantially to variations in rates of osteoporotic fracture risk in Europe.
Absorptiometry, Photon↗
Role of alfacalcidiol on bone quality and immunomodulation in autoimmune disease and organ transplantation.
In autoimmune diseases, as well as in organ transplantation, corticosteroids are often an obligatory part of the treatment regimen. The deleterious effect of corticosteroids on bone metabolism is well known, although still controversial [1-3]. It is easier to maintain bone mass than to restore it. Although the treatment of choice for prevention of bone loss is hormone replacement therapy, it cannot always be applied, and for many reasons compliance is low over the world. Alternative strategies to prevent bone loss are now tried out in many centers. Calcitonin and bisphosphonates are well-known antiresorbing drugs, but costs and long-term efficiency for calcitonin and fear for bone toxicity for the bisphosphonates limits their use for prevention. An attractive strategy to prevent osteoporosis is the treatment with alfacalcidiol because it is a natural product with important effects on bone metabolism in physiological and pharmacological dosages. Calcium absorption from the gut and mineralization of the bone matrix are optimalized by alfacalcidiol. The purpose of this paper is to report on our experience with alfacalcidiol concerning bone mass and quality in corticosteroid-induced osteoporosis in experimental animals and on long-term bone quality in autoimmune diseases and organ transplantation. We have studied the effects of alfacalcidiol on bone mass and quality in ovariectomized animals with and without corticosteroids. In these fundamental studies we have found that alfacalcidiol had a profound protective and curative effect not only on bone mass but also on bone quality as tested by mechanical testing, namely, impact torsional loading test of whole bones. The combination of alfacalcidiol with estrogens was less effective than alfacalcidiol, but more effective than estrogens alone [4-6] (Fig. 1).
Autoimmune Diseases↗
Factors associated with cortical and trabecular bone loss as quantified by peripheral computed tomography (pQCT) at the ultradistal radius in aging women.
Peripheral quantitative computed tomography (pQCT) allows the separate determination of cortical and trabecular bone mineral density in the peripheral skeleton. This cross-sectional study was designed to examine the effects of healthy aging on pQCT measurements at the ultradistal radius. In a well-defined sample of 129 community-based women, aged 70-87 years, the differences in cortical and trabecular density over the age range were equivalent to losses of -0.41% and -0.65% per year, respectively. To investigate the mechanism of this age-related decline, we assessed relationships between both parameters and height, weight, body mass index, dietary calcium intake, grip strength, and serum concentrations of insulin-like growth factor-I (IGF-I), calcidiol (25(OH)D3), calcitriol (1,25(OH)2D3), parathyroid hormone (PTH), and sex hormone binding globulin (SHBG). Multiple regression was used to adjust for potential confounders. Age was not significant after controlling for other covariables. Body mass index, grip strength, serum IGF-I, 25(OH)D3, and PTH (1-84) were found to be independent predictors of total bone density. Including (total or free) 1,25(OH)2D3 did not improve the model precision. These findings provide evidence that, among other factors, the activity of the growth hormone-IGF-I-axis is of importance for skeletal integrity. Grip strength, serum IGF-I, and PTH (1-84) were discovered to be significantly related to cortical but not to trabecular density, suggesting that different mechanisms may be involved in compact and cancellous bone loss.
Aged↗
Prevalence of trabecular microcallus formation in the vertebral body and the femoral neck.
Trabecular microcallus formation (TMF) has been described previously in the human vertebra and femur, but the difference in TMF prevalence at these two sites has not been studied and the role of TMF remains controversial. In this study, the 4th lumbar vertebra (L4) and right proximal femur were removed from 27 male and 23 female cadavers. A 2 cm cube cut from the center of L4 and a 1 cm-thick slice cut from the femoral neck were cleaned, defatted, and dried. The apparent density of the L4 cubes was determined as dry weight/bulk bone volume. Using a dissecting microscope at low magnification (4-60x), TMF were identified and counted in both the vertebral and femoral samples. A 8 mm diameter core was then cut from the center of the L4 cubes in the vertical direction, and selected histomorphometric parameters of the core were evaluated with an X-ray microcomputed tomography system (micro-CT). There was a significantly greater prevalence of TMF in vertebral cubes (82%) than in the femoral slices (11%) (P < 0.001). TMF prevalence did not differ significantly between males and females, but the mean number of TMF in the vertebra was significantly (P < 0.05) greater in females (15.0/vertebra) than in males (7.7/vertebra). In the vertebra, the majority of the observed TMF were in vertical trabeculae. Subjects over 60 years old had a higher TMF prevalence than those under 60 years old (P < 0.01). TMF numbers increased with decreasing apparent density (P < 0.05), whereas no significant correlations were found between TMF and bone volume (BV/TV), trabecular number (Tb.N), or trabecular thickness (Tb.Th) as assessed by micro-CT. In two fractured vertebra, very few TMFs (2 and 4, respectively) were observed. These results demonstrated that the occurrence of TMF is strongly related to the anatomical site, probably due to differences in the applied loads and the trabecular structure between sites. The results were consistent with the hypothesis that TMF is a mechanism acting to maintain bone strength, but further studies are needed to clarify this important issue.
Adult↗
Age-associated decline in human femoral neck cortical and trabecular content of insulin-like growth factor I: potential implications for age-related (type II) osteoporotic fracture occurrence.
Recent evidence suggests that regulatory peptides such as insulin-like growth factor-I (IGF-I) are released locally from bone during resorption, and may then act in a sequential manner to regulate the cellular events required for the coupling of bone formation to resorption. Among other factors, a decrease in bone-associated IGF-I levels could therefore result in remodeling imbalance and contribute to the gradual loss of bone that occurs with age. As the femoral neck region is of primary concern for the clinical manifestations of osteoporosis, the current study was intended to assess the IGF-I contents in femoral neck cortical and trabecular bone from aging individuals. Bone samples from the neck region were obtained at postmortem from 39 females and 35 males, aged 23-92 years. Concentrations of IGF-I and osteocalcin were measured by radioimmunoassay in the supernatants obtained after EDTA and guanidine hydrochloride extraction. The total amount of protein present in the extracts was determined by spectrophotometry. IGF-I levels were significantly lower in trabecular compared with cortical bone. Though femoral neck total protein did not vary with donor age, both IGF-I and osteocalcin were found to decline markedly. Between the ages of 23 and 92 years, average yearly rates of loss of 0.30 and 0.21 ng IGF-I/mg protein were observed in cortical and trabecular bone, respectively, corresponding with net losses of nearly 35% of the cortical skeletal content of IGF-I and 41% of the trabecular skeletal content of IGF-I. These changes in bone-associated IGF-I paralleled those of osteocalcin, consistent with an overall decrease in osteoblast function with aging. In women, the rate of decline was significantly faster for trabecular than for cortical IGF-I, however in men, age-dependent changes in cortical and trabecular IGF-I were similar. These findings support the hypothesis that changes in the local IGF regulatory system over time could be a pathophysiologic component of the age-related (type II) femoral neck osteoporotic syndrome.
Adult↗