Josefina Martínez

Trend in hip fracture epidemiology over a 14-year period in a Spanish population

Spain lacks detailed data on hip fracture trends despite being the country with the greatest increase in the pensioner-to-provider ratio in Europe. We reproduced a study on hip fracture incidence in a region of northern Spain (Cantabria) carried out 14 years ago to determine whether a secular trend to change is taking place. If such a trend could be found, our objective was to determine whether the effect is solely due to ageing or whether additional variables are involved. We assessed the incidence of hip fracture in patients aged ≥50 years through clinical records from Emergency Units and Orthopedic Surgical Units of all hospitals in the region of Cantabria in 1988 and 2002. A total of 318 new cases of hip fracture were recorded in 1988 and 490 in 2002 (54% increase; p<0.001). No significant changes were noticed following an adjustment for age. Women accounted for the increase in crude hip fracture incidence [246 women and 72 men suffered a hip fracture in 1988 compared to 404 women and 86 men in 2002 (64% increase in women and 19% increase in men; p<0.005 and not significant, respectively)]. The female:male ratio was 3.4 in 1988 versus 4.7 in 2002; following age-adjustment, no significant changes were found (1.8 in 1988 and 1.9 in 2002). The increase in crude hip fracture incidence was greater at cervical (versus trochanteric) sites. Patient residence, time of the year, site of fracture, kind of injury, previous contralateral hip fracture, length of stay, and peri-operative mortality did not differ significantly. In conclusion, a crude hip fracture incidence increase of about 50% in the northern Spanish region of Cantabria has taken place over the last 14 years. This effect does not persist after adjustments have been made for age. The crude rate increase occurred mainly at the expense of women, with a more noticeable rise in cervical fractures as opposed to trochanteric lesions.

Metabolic syndrome and bone metabolism: the Camargo Cohort Study

Objectives: The aims of this study were to compare in participants with and without metabolic syndrome (1) bone mineral density (BMD), (2) prevalent vertebral and nonvertebral fractures, and (3) calciotropic hormones and bone turnover markers and to examine the association of each component of metabolic syndrome with bone parameters. Methods: A cross-sectional study (495 men and 1,013 women) from the Camargo Cohort Study was conducted. A multivariable regression approach was used to analyze the relationship between the components of metabolic syndrome and bone parameters. Results: Women with metabolic syndrome had higher age-adjusted BMD at all localizations (P < 0.0001) than did women without metabolic syndrome. Adjusting for body mass index canceled out this difference at the spine and femoral neck, although borderline significance persisted at the total hip. Moreover, in regression analyses, waist circumference (P < 0.0001) and hypertension (P between 0.002 and <0.0001) highly correlated with BMD at the three sites. However, no significant differences in BMD were found in men between those with and without metabolic syndrome. No differences in the prevalence of vertebral or nonvertebral fractures between participants with metabolic syndrome and controls were found for either sex. 25-Hydroxyvitamin D was significantly lower (P < 0.0001) and parathyroid hormone was significantly higher (P < 0.0001) in women with metabolic syndrome than in women without metabolic syndrome, whereas no differences were seen in men. Propeptide of type I collagen and C-terminal telopeptide of type I collagen were significantly lower in participants with metabolic syndrome than in controls in either sex. Conclusions: Women with metabolic syndrome show higher BMD than controls do, mainly driven by their higher body weight. Bone remodeling in these women is lower. Despite the greater bone mass and lower bone turnover, fracture prevalence is not reduced, suggesting worse bone quality and/or higher tendency to fall. No differences in BMD or fractures were seen in men, suggesting that the impact of metabolic syndrome on bone is sex dependent.

Bone turnover markers in Spanish postmenopausal women The Camargo cohort study

BACKGROUND This cross-sectional study was performed to determine the reference ranges for two bone turnover markers--aminoterminal propeptide of type I collagen (P1NP) and C-terminal telopeptide of type I collagen (beta-CrossLaps, beta-CTX)--in normal postmenopausal Spanish women as determined in serum by automated methods. METHODS A community-based population of 1080 healthy postmenopausal women was evaluated. Data regarding risk factors for osteoporosis and fractures were collected by means of a structured questionnaire. Fasting serum levels of P1NP, beta-CTX, 25-Hydroxivitamin D (25OHD), and intact parathyroid hormone (iPTH) were measured on the Elecsys 2010 automated analyzer (Roche). BMD at lumbar spine, femoral neck and total hip was determined by DXA. RESULTS The mean age of subjects was 63+/-9. Logarithmic transformation of both markers was performed to allow for normal distributions. Mid-95% ranges for P1NP and beta-CTX were 19-100 ng/ml and 0.112-1.018 ng/ml, respectively. Mean values of P1NP (47.7+/-19.9 ng/ml) were similar to those previously determined by the manufacturer of the assays, whereas beta-CTX mean values (0.387+/-0.197 ng/ml) were lower. Both markers were higher among osteoporotic women. CONCLUSIONS Values obtained from this well-characterized population study provide reference ranges for serum automated P1NP and beta-CTX in normal Spanish postmenopausal women.

Bone turnover markers in Spanish adult men The Camargo Cohort Study

BACKGROUND This cross-sectional study was performed to determine the reference ranges for two bone turnover markers-aminoterminal propeptide of type I collagen (P1NP) and C-terminal telopeptide of type I collagen (beta-CTX)-in normal adult Spanish men as measured in serum by automated methods. METHODS A community-based population of 660 healthy men > or = 50 years was evaluated. Fasting serum levels of P1NP, beta-CTX, 25-hydroxyvitamin D, and intact parathyroid hormone were measured on the Elecsys 2010 automated analyzer (Roche). BMD at lumbar spine, femoral neck and total hip was determined by DXA. RESULTS Mean age of participants was 65 + or - 9 years. Logarithmic transformation of both markers was performed to allow for normal distribution. Mid-95% ranges for P1NP and beta-CTX were 15-78 ng/ml and 0.069-0.760 ng/ml, respectively. Median and interquartile range of serum P1NP and beta-CTX were 33.5 [25.5;44.4] ng/ml and 0.27 [0.19;0.38] ng/ml, respectively. Mean values of P1NP (37.1 + or - 16.7 ng/ml) were similar to those previously described. beta-CTX mean values (0.300 + or - 0.171 ng/ml) were also similar to those quoted by the manufacturers in men younger than 70 years, but slightly lower than those reported in subjects older than 70 years. Both markers were higher among osteoporotic men. After excluding from the analysis those men who were found to have BMD below -2.5 T-score, 25OHD serum level below 30 ng/ml or serum PTH above 65 pg/ml, P1NP and beta-CTX ranges were 17-71 ng/ml and 0.070-0.681 ng/ml, again respectively. CONCLUSIONS Values obtained from this well-characterized population study provide reference ranges for serum automated P1NP and beta-CTX in normal Spanish adult men.

Bone turnover markers and bone mineral density in hypertensive postmenopausal women on treatment

OBJECTIVE To evaluate bone mineral density (BMD) and bone metabolism in hypertensive postmenopausal women, and to differentiate the effect of thiazides from that of other antihypertensive agents. SUBJECTS AND METHODS A community-based population of 636 postmenopausal women, 293 with hypertension (160 receiving thiazides, and 133 receiving other antihypertensive treatments), and 343 control women, were evaluated. Serum levels of aminoterminal propeptide of type I collagen (P1NP), C-terminal telopeptide of type I collagen (beta-CTX), 25-hydroxivitamin D, and intact parathyroid hormone were measured by electrochemiluminiscence. BMD was determined by DXA, and heel quantitative ultrasound measurements (QUS) with a gel-coupled device. RESULTS BMD expressed as Z-score was higher in both groups of hypertensive women at all locations. Expressed as g/cm(2), it was also higher in patients on thiazides at femoral neck and lumbar spine. Only in the latter site, differences remained significant after adjusting for potential confounding variables, including BMI. Bone turnover markers were lower in both groups of hypertensive women, although the difference was greater in those on thiazides. After adjusting for potential confounders, differences remained significant only in the thiazide group. CONCLUSIONS Our results add evidence to the idea that thiazides are beneficial to prevent bone loss.

Influence of Vitamin D Status on Vertebral Fractures, Bone Mineral Density, and Bone Turnover Markers in Normocalcemic Postmenopausal Women With High Parathyroid Hormone Levels

OBJECTIVE The aims of the study were to analyze whether there is an association between serum PTH and the prevalence of vertebral fractures and its possible dependence on vitamin D status, and to assess the influence of serum 25-hydroxyvitamin D (25OHD) in the relationship between PTH and bone mineral density (BMD) or bone turnover markers (BTMs). DESIGN, PARTICIPANTS, AND SETTING A total of 820 postmenopausal women were recruited after excluding those with any known condition that could influence serum PTH levels, except for a possible low serum 25OHD. Serum PTH and 25OHD concentrations, as well as vertebral fracture prevalence, BMD, and BTM (CTX and PINP) values were recorded. Serum PTH levels were divided into tertiles, and women were grouped into those in the highest tertile (>58 pg/ml) and those below. Serum 25OHD levels were stratified in 3 categories (<20, 20-30, and >30 ng/ml). RESULTS Vertebral fracture prevalence was greater in women with PTH above 58 pg/ml (odds ratio [OR], 1.72; 95% confidence interval [CI], 1.04-2.84). After stratifying by 25OHD, this difference was only significant in women below 20 ng/ml (OR, 2.00; 95% CI, 1.02-3.87), those with 25OHD between 20 and 30 ng/ml showing a trend toward this (OR, 1.99; 95% CI, 0.92-4.36). Differences in BMD or BTM between women above and below 58 pg/ml of PTH were also observed only in those below 20 ng/ml. CONCLUSION Elevated PTH levels are associated with increased prevalence of vertebral fractures, low bone mass, or higher BTM only in the presence of hypovitaminosis D. An adequate nutritional status in the vitamin appears to protect the bone from the deleterious effect of a high PTH.

Heel quantitative ultrasound parameters in subjects with the metabolic syndrome: the Camargo Cohort Study.

OBJECTIVES To compare bone parameters measured by calcaneous quantitative ultrasonography (BUS) in subjects with and without metabolic syndrome (MetS). In addition, we wanted to examine the association of each of the individual components of the syndrome with BUS measurements, to study the relationship between calciotropic hormones or bone turnover markers with BUS parameters in subjects with or without MetS, and to explore the possibility that the relationship between prevalent vertebral and non-vertebral fractures and BUS is influenced by MetS status. STUDY DESIGN Cross-sectional study. RESULTS We investigated 1209 (421 men and 788 women) participants from the Camargo Cohort Study. Prevalence of MetS was 27% in men and 31% in women. Women, but not men, with MetS had higher age-adjusted BUS parameters compared with those without (p<0.05), the difference disappearing after adjustment for BMI. Out of the five single components of MetS, only waist perimeter was significantly associated with BUS (p<0.01), the association being restricted to women. In men and women with MetS (but not without) a positive significant association was observed between BUS and 25OHD levels. BUS parameters were associated with serum P1NP or CTX in normal women, but not in those with MetS. Prevalent vertebral and non-vertebral fractures and BUS parameters (BUA and SOS, respectively) are inversely associated, but this relationship, however, is not influenced by MetS status. CONCLUSIONS BUS parameters are higher in women with MetS, and this difference disappears after adjusting for BMI. MetS status did not influence the relationship between BUS parameters and vertebral or non-vertebral fractures.

Influence of Vitamin D Status on the Effect of Statins on Bone Mineral Density and Bone Turnover Markers in Postmenopausal Women

OBJECTIVE This study sought to assess whether the association between statin use and bone mineral density (BMD) and bone turnover markers is modulated by serum 25-hydroxyvitamin D (25OHD) levels in postmenopausal women. Design, Participants, and Settings: Approximately 1422 postmenopausal women were recruited from the Camargo Cohort after excluding those with any known medical disorder or drug that might affect bone metabolism. Participants were categorized into four groups: 25OHD levels of 20 ng/mL or less and not taking statins (group 1; n = 492); 25OHD levels greater than 20 ng/mL and on statins (group 2; n = 143); 25OHD levels of 20 ng/mL or less and using statins (group 3; n = 112); and 2OHD levels greater than 20 ng/mL and non-statin use (group 4; n = 675). Multivariate analyses were performed to compare BMD and bone turnover markers between groups. RESULTS Women in group 2 had an adjusted femoral neck and total hip BMD higher than women in group 1 (P < .0001 and P = .003, respectively). A trend toward a significant difference was observed regarding lumbar BMD (P = .08). Serum aminoterminal propeptide of type 1 collagen and C-terminal telopeptide of type 1 collagen levels were lower in group 2 than in group 1, in crude and adjusted models, although only serum C-terminal telopeptide of type 1 collagen difference was significant (P = .009). CONCLUSIONS Women on statins and serum 25OHD levels above 20 ng/mL have greater BMD and less bone resorption than those without either of the factors. Differences, however, are not significant in women with only one of them. Vitamin D and statins seem to interact positively in their effects on bone metabolism.

1,25-Dihydroxyvitamin D3 receptors in peripheral blood mononuclear cells from patients with primary and secondary hyperparathyroidism.

A decreased number of calcitriol (1,25(OH)2D3) receptors has been observed in parathyroid glands of uremic animals. In humans, studies carried out in surgically removed parathyroid glands have shown that calcitriol binding is higher in primary than in secondary hyperparathyroidism. Since specific receptors for calcitriol have been described in peripheral blood mononuclear cells (PBMC), we have investigated the specific uptake of 3H-labelled 1,25(OH)2D3 in PBMC of 12 women with primary hyperparathyroidism (PHP), 8 women with hyperparathyroidism secondary to chronic renal failure (SH), 9 women with renal transplant (RT), and 23 healthy women. The median dissociation constant (Kd) was similar in all three groups of patients and in healthy women (mean +/- S.D. (range): PHP, 1.2 +/- 1.0 (0.2-4) x 10(-10) M; SH, 0.6 +/- 0.4 (0.2-1.2) x 10(-10) M; RT, 1.1 +/- 0.5 (0.4-1.9) x 10(-10) M; controls, 1.0 +/- 0.6 (0.3-2.6) x 10(-10) M). However, the maximal binding capacity (Nmax) was significantly enhanced in PHP (3.9 +/- 1.9 (1.3-7.6) fmol/10(7) cells vs. 2.3 +/- 0.9 (1.1-4.4) fmol/10(7) cells in controls; P = 0.0006) and decreased in SH (0.8 +/- 0.5 (0.2-1.6) fmol/10(7) cells vs. 2.3 +/- 0.9 (1.1-4.4) fmol/10(7) cells in controls; P = 0.0001), whereas no changes were seen in RT (2.3 +/- 0.7 (1.2-3.3) fmol/10(7) cells vs. 2.3 +/- 0.9 (1.1-4.4) fmol/10(7) cells in controls). In three patients with PHP who were subjected to parathyroidectomy, the calcitriol number came down to normal. Changes of calcitriol receptors in primary and secondary hyperparathyroidism could magnify the consequences of disturbances in serum concentration of calcitriol itself and might play an important role in the development of secondary hyperparathyroidism in uremia.

Bone turnover markers in statin users: A population-based analysis from the Camargo Cohort Study

OBJECTIVE To analyze the effects of statin use on bone turnover markers (BTM), in participants from a large population-based cohort. SUBJECTS AND METHODS Cross-sectional study that included 2431 subjects (1401 women and 930 men) from the Camargo Cohort. We analyzed the differences in serum BTM between statin or non-statin users, by means of a generalized linear model, adjusted for a wide set of covariates and stratified by diabetes status. We also studied the effect of the type of statin, dose, pharmacokinetic properties, and length of treatment, on BTM. RESULTS Five hundred subjects (21%) were taking statins (273 women and 227 men). Overall, they had lower levels of aminoterminal propeptide of type I collagen (PINP) and C-terminal telopeptide of type I collagen (CTX) than non-users (p<0.0001). BTM levels were significantly lower in diabetic women using statins, than in female non-statin users with diabetes. In men, we found similar results, but only for CTX. All the statins users had lower levels of BTM than non-users, except subjects taking fluvastatin that showed slightly higher values. In the whole sample, no differences between dose or drug-potency were noted regarding BTM. When comparing with non-statin users, only subjects taking lipophilic statins had lower BTM levels (p<0.0001). Serum CTX levels were lower in women using statins for more than 3 vs. 1-3 years (p=0.006). CONCLUSIONS In a large population-based cohort, serum BTM were lower in participants taking statins than in non-users, and this effect was modulated by diabetes status. Overall, this decrease in BTM was more evident in subjects receiving the more lipophilic statins, especially when using for more than 3 years.