Vulnerability of healthy vertebrae in patients with and without previous vertebral fracture.

Vertebral deformities are associated with a marked increase in morbidity, mortality, and burden in terms of sanitary expenditures. Patients with vertebral fractures have a negative impact in their health, less quality of life, and loss of functional capacity and independence. The purpose of this study was to explore the vulnerability of healthy vertebrae in patients who have sustained already a compression fracture and in patients who do not have prevalent fractures in the thoracic spine; and to explore the association of the deformity in healthy vertebrae with different variables, such as bone mineral density (BMD), body mass index, age, loss of height, presence of clinical kyphosis, history of other osteoporotic fractures, and falls occurring during the last year. Clinical data and complementary studies from 175 postmenopausal outpatients were analyzed. These women (age: 69.7±11.1 years) had not received any treatment for osteoporosis. Anteroposterior and lateral radiographs of the thoracic spine and bone densitometry of the hip were obtained; morphometry was performed in 1575 thoracic vertebrae from T4 to T12. The angle of wedging of each vertebral body was calculated using a trigonometric formula. Then, the sum of wedge angles of vertebral bodies (SWA) was determined, and Cobb angle was measured. In patients with vertebral fractures, after excluding the angles of fractured vertebral bodies, the mean wedge angle of the remaining vertebrae (MWAhealthy) was calculated. The same procedure was followed in patients without vertebral fractures. MWAhealthy was considered as an indicator of the structural vulnerability of non-fractured vertebrae. Patients with prevalent fractures had lower BMD, wider Cobb angle, and higher sum of wedge angles than patients without vertebral fractures. The proportion of patients with accentuation of clinical kyphosis was higher in the group with prevalent vertebral fractures. A highly significant difference was found in the MWAhealthy, which was higher in patients with prevalent fractures (4.1±1.3° vs. 3.0±1.1°; p<0.001). Patients showing vertebral fractures had 7.1±4.2 cm height loss in average, significantly superior than that found among non-fractured women (3.6±3.2 cm; p<0.01). In multivariate analysis, the increase of MWAhealthy was associated with advancing age (p<0.02), lower femoral neck BMD (p<0.005), presence of clinical kyphosis (p<0.01) and vertebral fractures (p<0.02). This study presents evidence that a series of factors independently influence the increase in wedging deformity of vertebral bodies that are not fractured yet. These factors could contribute to an increased vulnerability of the vertebrae, making them more susceptible to fracture.

Age at menopause in Latin America.

OBJECTIVE: To assess the age at menopause (AM) in Latin America urban areas. DESIGN: A total of 17,150 healthy women, aged 40 to 59 years, accompanying patients to healthcare centers in 47 cities of 15 Latin American countries, were surveyed regarding their age, educational level, healthcare coverage, history of gynecological surgery, smoking habit, presence of menses, and the use of contraception or hormone therapy at menopause. The AM was calculated using logit analysis. RESULTS: The mean age of the entire sample was 49.4 +/- 5.5 years. Mean educational level was 9.9 +/- 4.5 years, and the use of hormone therapy and oral contraception was 22.1% and 7.9%, respectively. The median AM of women in all centers was 48.6 years, ranging from 43.8 years in Asuncion (Paraguay) to 53 years in Cartagena de Indias (Colombia). Logistic regression analysis determined that women aged 49 living in cities at 2,000 meters or more above sea level (OR = 2.0, 95% CI: 1.4-2.9, P < 0.001) and those with lower educational level (OR = 1.9, 95% CI: 1.3-2.8, P < 0.001) or living in countries with low gross national product (OR = 2.1, 95% CI: 1.5-2.9, P < 0.001) were more prone to an earlier onset of menopause. CONCLUSIONS: The AM varies widely in Latin America. Lower income and related poverty conditions influence the onset of menopause.

Construction of two instruments for the presumptive detection of post-menopausal women with low spinal bone mass by means of clinical risk factors.

The objective of this investigation was the design of two instruments based on clinical risk factors for the presumptive detection of post-menopausal women with spinal BMD<2.5 S.D. below average (LBMD). We investigated the association of 20 risk factors (RF) with LBMD in a series of 131 women. According to current densitometric criteria, subjects were classified as normals (N=33); osteopenics (N=53) and osteoporotics (N=45). Normals and osteopenics were taken as a single group because only 'nulliparity' and 'personal fractures' exhibited significant differences between these groups. A logistic regression attempting to identify which factors were associated with osteopenia showed a poor fit (pseudo R(2)=0.289). Univariate unconditional logistic regression analysis was used to calculate odd ratios (ORs) and their 95% CI for all RF. Those with associated P-values <0.100 were included in a multivariate logistic regression analysis to obtain the odds ratios (OR) adjusted by the effects of the others. The variables with not significant beta coefficients were eliminated, producing a reduced model. BMI (<25 kg/m(2)), calcium intake (<1.2g/day), menopause (>10 years), and the simultaneous occurrence of kyphosis and personal fractures showed significant association with low bone mass at the lumbar spine and their effect was additive. Fitting of the data to the model was assessed with the Hosmer-Lemeshow test (P=0.926) The area under the ROC curve is 0.833 (95% CI=0.757-0.909). The following equation calculates the probability of having low spinal bone mass: The sensitivity, specificity and area under the ROC curve were defined. The point of maximum specificity and sensitivity derived from the ROC curve, has a probability of 0.409. With such a cut-off point, the equation has a sensitivity of 73%, specificity 79%, positive predictive value 65% and negative predictive value 85%. The second instrument associates very low lumbar bone mass with the number of risk factors accumulated per patient. At baseline, all subjects had four RFs: they were, women, white, post-menopausal, and with no previous exposure to estrogens. With six additional RFs the presumptive diagnosis of LBMD has a specificity of 99%, positive predicting value 94% and false positives 6.5%. The area under the curve in a ROC graph was 0.826 (95% CI=0.747-0.914). Comparing present instruments with others in the literature, it is concluded that each population require its own algorithm for the presumptive detection of subjects with low bone mass. The algorithm should be reassessed periodically if the characteristics of the population or its social-economic conditions change.

In postmenopausal osteoporosis the bone increasing effect of monofluorophosphate is not dependent on serum fluoride

According to previous pharmacokinetic studies the biovailability of fluorine (F) from sodium monofluorophosphate (MFP) doubles that of sodium fluoride (NaF). This paper reports a study designed to verify whether the vertebral bone mass increasing effect of NaF (30 mg F/day) was comparable to that of MFP (15 mg F/day), given for 18 months to osteoporotic postmenopausal women. The BMD of lumbar vertebrae of both groups showed significant increases (MFP: 60 + 15 mg/cm2, NaF: and 71 + 12 mg/cm2) over basal levels (P < 0.001). The difference between treatments was not significant (P = 0.532). The serum levels of ionic F (the mitogenic species on osteoblasts) were not related to the above mentioned effects. In NaF-treated patients, the fasting levels of total serum F increased significantly (6.7 + 0.9 muM vs. Basal: 2.0 + 0.8 muM; P < 0.001). This phenomenon was accounted for by ionic fluoride that increased over 20-fold (6.5 + 1.9 muM vs. Basal: 0.3 + 0.04 muM). In MFP-treated patients the fasting serum levels of total (7.0 + 0.7 muM vs. Basal: 2.2 + 0.9 M) and diffusible F (0.5 + 0.02 muM vs. Basal 0.2 + 0.02 muM) increased significantly (P < 0.001). The increase in the non diffussible F fraction is accounted for by proteinboud F, probably by the complexes formed between MFP and alpha2-macroglobulin and C3. Serum diffusible F was formed by two fractions: ionic F and F bound to low molecular weight macromolecule/s (2 200 + 600 Da), in approximately equal amounts. The general information afforded by the present observations support the hypothesis that ionic F is released progressively during the metabolism of MFP bound to alpha2-macroglobulin and C3. These phenomena explain why comparable effects to those obtained with 30 mg F/d of NaF could by obtained with one half the dose of MFP.

In postmenopausal osteoporosis the bone increasing effect of monofluorophosphate is not dependent on serum fluoride

According to previous pharmacokinetic studies the biovailability of fluorine (F) from sodium monofluorophosphate (MFP) doubles that of sodium fluoride (NaF). This paper reports a study designed to verify whether the vertebral bone mass increasing effect of NaF (30 mg F/day) was comparable to that of MFP (15 mg F/day), given for 18 months to osteoporotic postmenopausal women. The BMD of lumbar vertebrae of both groups showed significant increases (MFP: 60 + 15 mg/cm2, NaF: and 71 + 12 mg/cm2) over basal levels (P < 0.001). The difference between treatments was not significant (P = 0.532). The serum levels of ionic F (the mitogenic species on osteoblasts) were not related to the above mentioned effects. In NaF-treated patients, the fasting levels of total serum F increased significantly (6.7 + 0.9 muM vs. Basal: 2.0 + 0.8 muM; P < 0.001). This phenomenon was accounted for by ionic fluoride that increased over 20-fold (6.5 + 1.9 muM vs. Basal: 0.3 + 0.04 muM). In MFP-treated patients the fasting serum levels of total (7.0 + 0.7 muM vs. Basal: 2.2 + 0.9 M) and diffusible F (0.5 + 0.02 muM vs. Basal 0.2 + 0.02 muM) increased significantly (P < 0.001). The increase in the non diffussible F fraction is accounted for by proteinboud F, probably by the complexes formed between MFP and alpha2-macroglobulin and C3. Serum diffusible F was formed by two fractions: ionic F and F bound to low molecular weight macromolecule/s (2 200 + 600 Da), in approximately equal amounts. The general information afforded by the present observations support the hypothesis that ionic F is released progressively during the metabolism of MFP bound to alpha2-macroglobulin and C3. These phenomena explain why comparable effects to those obtained with 30 mg F/d of NaF could by obtained with one half the dose of MFP. (AU)

Outcome of hip fractures among elderly subjects

This paper reports a retrospective study (1979-1995) on 200 patients (154 women and 46 men), 50-101 years old, who received medical attention because of unilateral hip fracture. Nine women and four men fractured twice. In 75 percent of women and 90 percent of men, surgery was carried out between one and five days after fracture. A non significant greater proportion of women (14/154) than men (6/46) died in the first year after injury (X2=3.459, P = 0.062). Survival was assessed using Cox proportional hazards model. Survival was a function of age (P = 0.000) and sex (P = 0.008). After adjustment to a common mean age (79 years), the median survivals for men and women were 3.9 and 8.4 years, respectively. Controlled concurrent life-threatening diseases, the king of fracture [medial (subcapital and transcervical) or lateral (inter- and subtrochanteric)] and the type of prosthesis (total/partial articulation replacement) had no significant impact on survival. No differences in evolution were observed: 80 percent returned to their ambulatory status before injury, 8.5 percent required walking aids and 5.5 percent could not walk. The overall information afforded by this study suggests that with worldwide improvement of hip fracture outcome, the cost/effectiveness of surgical treatment of hip fracture may become, from the standpoint of public health investment, a favorable alternative with respect of cost/effectiveness of prevention-treatment measures.

Outcome of hip fractures among elderly subjects

This paper reports a retrospective study (1979-1995) on 200 patients (154 women and 46 men), 50-101 years old, who received medical attention because of unilateral hip fracture. Nine women and four men fractured twice. In 75 percent of women and 90 percent of men, surgery was carried out between one and five days after fracture. A non significant greater proportion of women (14/154) than men (6/46) died in the first year after injury (X2=3.459, P = 0.062). Survival was assessed using Cox proportional hazards model. Survival was a function of age (P = 0.000) and sex (P = 0.008). After adjustment to a common mean age (79 years), the median survivals for men and women were 3.9 and 8.4 years, respectively. Controlled concurrent life-threatening diseases, the king of fracture [medial (subcapital and transcervical) or lateral (inter- and subtrochanteric)] and the type of prosthesis (total/partial articulation replacement) had no significant impact on survival. No differences in evolution were observed: 80 percent returned to their ambulatory status before injury, 8.5 percent required walking aids and 5.5 percent could not walk. The overall information afforded by this study suggests that with worldwide improvement of hip fracture outcome, the cost/effectiveness of surgical treatment of hip fracture may become, from the standpoint of public health investment, a favorable alternative with respect of cost/effectiveness of prevention-treatment measures. (AU)