[Phototype, vitamin D status and bone mineral density among women at risk of osteoporosis]. / Phototype, statut en vitamine D et densité minérale osseuse chez des femmes à risque d'ostéoporose.

PURPOSE: The aim of this study was to test the influence of phototype and vitamin D status feature on the bone mineral density (BMD) of the femoral neck in a group of middle-aged women considered at risk of osteoporosis (low levels of vitamin D [25(OH)D3<78 nmol/L] and hyperparathyroidism [parathormone level>36 pg/mL]). METHODS: This two-step study was conducted on 122 French women enrolled in the SUVIMAX (supplémentation en vitamines et minéraux antioxydants: antioxidant vitamin and mineral supplementation) cohort. The impact of various variables on BMD, including age, body mass index (BMI), vitamin D status, alcohol intake, sun exposure intensity and phototype was investigated using regression models. RESULTS: No statistical link was found between BMD and the variables documenting vitamin D status and parathormone levels, nor phototype. Nevertheless, fair phototypes tended to be associated with lower BMD values. However, BMD decreased with age and increased with BMI and physical activity level. CONCLUSIONS: Whatever their phototype, adult women concerned about precarious vitamin D status should undergo a vitamin D supplementation in combination with an adequate calcium intake all year long and a proper sun protection. Moreover, a physical activity maintenance should provide an additional benefit for prevention of osteoporosis.

Role of vitamin D and parathyroid hormone in the regulation of bone turnover and bone mass in men: the MINOS study.

We investigated the role of vitamin D and of parathyroid hormone (PTH) in the regulation of bone mineral density (BMD), tone dimensions and seasonal variation of bone turnover in 881 men aged 19-85 years. Bone mineral content (BMC) and BMD of the lumbar spine, hip and whole body were measured with HOLOGIC 1000W and those of distal forearm with an OSTEOMETER DTX 100 device. Bone formation was evaluated using osteocalcin, bone alkaline phosphatase and N-terminal extension propeptide of type I collagen (PINP). Bone resorption was evaluated by 24-hour excretion of deoxypyridinoline and of C-terminal telopeptide of collagen type I. In young men (< 55 yrs) PTH level decreased with age (r = -0.18, P < 0.005) whereas 25-hydroxyvitamin D (25OHD) concentration was stable. In older men (> 55 years) 25OHD decreased whereas PTH increased with age (r = -0.27 and r = 0.21, P = 0.0001). In young men, 25OHD level varied with season but not PTH, biochemical markers of bone turnover nor BMD. In young men, 25OHD, but not PTH, was a significant determinant of BMC, cortical thickness and of biomechanical properties of the femoral neck. Biochemical bone markers and BMD were not correlated with PTH nor with 25OHD. In elderly men, winter levels of 25OHD were lowest whereas those of PTH, bone resorption markers and PINP were highest. After adjustment for age, body weight and season, biochemical markers of bone turnover were correlated with PTH. In elderly men, 25OHD and PTH were significant determinants of BMC, cortical thickness and of biomechanical parameters of the femoral neck. Men with vertebral deformities had lower concentrations of 25OHD, higher PTH levels and slightly elevated urinary excretion of biochemical markers of bone resorption compared with men without vertebral deformities. In conclusion, in young men, 25OHD discloses a seasonal variability in contrast to PTH and biochemical bone markers. In this group, 25OHD is a significant determinant of BMC and BMD but not of bone size. In elderly men, seasonal variation of 25OHD and PTH concentrations result in seasonal variation of bone resorption. In this group, both 25OHD and PTH are determinants of BMC and cortical thickness of the femoral neck and, consequently, of its mechanical parameters.

Combined calcium and vitamin D3 supplementation in elderly women: confirmation of reversal of secondary hyperparathyroidism and hip fracture risk: the Decalyos II study.

Vitamin D insufficiency and low calcium intake contribute to increase parathyroid function and bone fragility in elderly people. Calcium and vitamin D supplements can reverse secondary hyperparathyroidism thus preventing hip fractures, as proved by Decalyos I. Decalyos II is a 2-year, multicenter, randomized, double-masked, placebo-controlled confirmatory study. The intention-to-treat population consisted of 583 ambulatory institutionalized women (mean age 85.2 years, SD = 7.1) randomized to the calcium-vitamin D3 fixed combination group (n = 199); the calcium plus vitamin D3 separate combination group (n = 190) and the placebo group (n = 194). Fixed and separate combination groups received the same daily amount of calcium (1200 mg) and vitamin D3 (800 IU), which had similar pharmacodynamic effects. Both types of calcium-vitamin D3 regimens increased serum 25-hydroxyvitamin D and decreased serum intact parathyroid hormone to a similar extent, with levels returning within the normal range after 6 months. In a subgroup of 114 patients, femoral neck bone mineral density (BMD) decreased in the placebo group (mean = -2.36% per year, SD = 4.92), while remaining unchanged in women treated with calcium-vitamin D3 (mean = 0.29% per year, SD = 8.63). The difference between the two groups was 2.65% (95% CI = -0.44, 5.75%) with a trend in favor of the active treatment group. No significant difference between groups was found for changes in distal radius BMD and quantitative ultrasonic parameters at the os calcis. The relative risk (RR) of HF in the placebo group compared with the active treatment group was 1.69 (95% CI = 0.96, 3.0), which is similar to that found in Decalyos I (RR = 1.7; 95% CI = 1.0, 2.8). Thus, these data are in agreement with those of Decalyos I and indicate that calcium and vitamin D3 in combination reverse senile secondary hyperparathyroidism and reduce both hip bone loss and the risk of hip fracture in elderly institutionalized women.

Relationship between vitamin D status and skin phototype in general adult population.

A link between bone mineral density and skin color has been reported recently, and pigmentation has been shown to affect cutaneous vitamin D production. In the present study, we investigated the relationship between phototype, global self-assessed sun exposure, geographical location and vitamin D serum levels in 1191 French adults. When the factors were analyzed separately, individuals with lower phototypes as well as those with lower sun exposure showed significantly lower levels of vitamin D than those with darker phototypes or those with higher sun exposure. However, when factors were analyzed as a whole, the vitamin D status was no longer linked with the phototype, but with sun exposure and geographical location. Since phototypes and global self-assessments of sun exposure were positively linked, our data suggest that lower vitamin D levels in fair-skinned individuals are due to their sun exposure behavior.

An international comparison of serum 25-hydroxyvitamin D measurements.

Vitamin D status is usually assessed by measuring the serum 25-hydroxyvitamin D (25(OH)D) concentration. This mainly depends on sunshine exposure, nutrition and age. Interlaboratory variation may hamper comparison between results from different populations. This study reports cross-calibration of the 25(OH)D assays of five laboratories. In study 1, serum 25(OH)D was measured with three different assays in 104 serum samples from a large vitamin D supplementation study. The mean serum 25(OH)D level was 80% higher when measured by competitive protein binding (CPB) assay than by high-performance liquid chromatography (HPLC), while radioimmunoassay (RIA) gave intermediate values. The highest correlation was observed between RIA and HPLC (r = 0.84, p <0.01). Of the serum 25(OH)D values in the lowest quartile by HPLC, 25% were not recognized by CPB and 21% were not recognized by RIA as belonging to the lowest quartile. In study 2, the five laboratories analyzed serum 25(OH)D in eight serum samples covering the concentration range very low to high, with five different assays. The differences between the mean values for serum 25(OH)D between the laboratories with the highest and lowest values was 38%. The ranking order of individual samples according to the serum 25(OH)D value was very similar in all laboratories. The results show that 25(OH)D values from different laboratories can not be assumed to be comparable unless a careful cross-calibration has been performed.

Prevalence of vitamin D insufficiency in an adult normal population.

The vitamin D status of a general adult urban population was estimated between November and April in 1569 subjects selected from 20 French cities grouped in nine geographical regions (between latitude 43 degrees and 51 degrees N). Major differences in 25-hydroxyvitamin D (25(OH)D) concentration were found between regions, the lowest values being seen in the North and the greatest in the South, with a significant 'sun' effect (r = 0.72; p = 0.03) and latitude effect (r = -0.79; p = 0.01). In this healthy adult population, 14% of subjects exhibited 25(OH)D values < or = 30 nmol/l (12 ng/ml), which represents the lower limit (< 2 SD) for a normal adult population measured in winter with the same method (RIA Incstar). A significant negative correlation was found between serum intact parathyroid hormone (iPTH) and serum 25(OH)D values (p < 0.01). Serum iPTH held a stable plateau level at 36 pg/ml as long as serum 25(OH)D values were higher than 78 nmol/l (31 ng/ml), but increased when the serum 25(OH)D value fell below this. When the 25(OH)D concentration became equal to or lower than 11.3 nmol/l (4.6 ng/ml), the PTH values reached the upper limit of normal values (55 pg/ml) found in vitamin D replete subjects. These results showed that in French normal adults living in an urban environment with a lack of direct exposure to sunshine, diet failed to provide an adequate amount of vitamin D. It is important to pay attention to this rather high prevalence of vitamin D insufficiency in the general adult population and to discuss the clinical utility of winter supplementation with low doses of vitamin D.

Markers of bone resorption predict hip fracture in elderly women: the EPIDOS Prospective Study.

Increased bone turnover has been suggested as a potential risk factor for osteoporotic fractures. We investigated this hypothesis in a prospective cohort study performed on 7598 healthy women more than 75 years of age. One hundred and twenty-six women (mean years 82.5) who sustained a hip fracture during a mean 22-month follow-up were age-matched with three controls who did not fracture. Baseline samples were collected prior to fracture for the measurement of two markers of bone formation and three urinary markers of bone resorption: type I collagen cross-linked N- (NTX) or C-telopeptide (CTX) and free deoxypyridinoline (free D-Pyr). Elderly women had increased bone formation and resorption compared with healthy premenopausal women. Urinary excretion of CTX and free D-Pyr, but not other markers, was higher in patients with hip fracture than in age-matched controls (p = 0.02 and 0.005, respectively). CTX and free D-Pyr excretion above the upper limit of the premenopausal range was associated with an increased hip fracture risk with an odds ratio (95% confidence interval) of 2.2 (1.3-3.6) and 1.9 (1.1-3.2), respectively, while markers of formation were not. Increased bone resorption predicted hip fracture independently of bone mass, i.e., after adjustment for femoral neck bone mineral density (BMD) and independently of mobility status assessed by the gait speed. Women with both a femoral BMD value of 2.5 SD or more below the mean of young adults and either high CTX or high free D-Pyr levels were at greater risk of hip fracture, with an odds ratio of 4.8 and 4.1, respectively, than those with only low BMD or high bone resorption. Elderly women are characterized by increased bone turnover, and some markers of bone resorption predict the subsequent risk of hip fracture independently of hip BMD. Combining the measurement of BMD and bone resorption may be useful to improve the assessment of the risk of hip fracture in elderly women.

Serum undercarboxylated osteocalcin is a marker of the risk of hip fracture: a three year follow-up study.

We have previously shown that elderly women with an increased serum undercarboxylated osteocalcin (ucOC) level have an increased risk of sustaining a hip fracture as compared to those with normal serum ucOC. We reassessed our findings on a larger number of hip fractures that occurred over 3 years in 183 institutionalized women (aged 70-97 years) belonging to a large prospective clinical trial. Total OC, carboxylated OC, ucOC, and alkaline phosphatase were significantly higher at baseline in those who sustained a hip fracture during the follow-up. The age-adjusted odds ratio for hip fracture was three times higher in women with increased ucOC at baseline (odds ratio = 3.1, 99.9% C.I. = 1.7-6.0, p < 0.001). In the logistic regression, ucOC was still predictive of the hip fracture when age and parathyroid hormone concentration were included into the model (odds ratio = 2.6, 95% C.I. = 1.05-6.4). These data confirm that ucOC is a marker of the increased risk of hip fracture in elderly institutionalized women. Serum ucOC may reflect some nutritional deficiency associated with increased bone fragility.

Healthy elderly French women living at home have secondary hyperparathyroidism and high bone turnover in winter. EPIDOS Study Group.

It was recently demonstrated that calcium and vitamin D supplements were capable of decreasing the incidence of hip fractures in institutionalized elderly subjects through a reduction of senile secondary hyperparathyroidism. As there are no appropriate data to recommend such a supplement to the elderly living at home, the aim of this study was to determine the incidence of senile secondary hyperparathyroidism in old French women from the general community, its relation to vitamin D status, and its contribution to bone turnover. Four hundred and forty women, aged 75-90 yr, were randomly selected from the general community by mailing from electoral listing in 5 French cities whose latitude varies from 49 degrees 9N to 43 degrees 6N. At the end of the winter, with previous hip fractures or those who were institutionalized were excluded. The results obtained in these women were compared to those obtained in 59 institutionalized old women and 54 younger healthy women. In the five cities for the women living at home, we found a mean PTH value greater than that obtained in young women (63 +/- 28 vs. 43 +/- 15 pg/ml; P = 0.001), but lower that that found in institutionalized women (76 +/- 49 pg/mL; P = 0.05). The mean 25-hydroxyvitamin D (25OHD) level was not different in subjects from the 5 cities, but in all of them it was significantly greater than that found in 59 institutionalized women (42.5 +/- 25.0 vs. 15.5 +/- 6.5 nmol/L; P = 0.0001) but lower than that in young adults (P < 0.001). The main determinants of PTH were in equal ratio, i.e. age (r = 0.19; P < 0.001), 25OHD, and, to a lesser degree, creatinine clearance (r = 0.10; P = 0.03). For 25OHD, the main determinant was the personal outdoor score and, to a lesser extent, the amount of daily sunlight in the city. The mean values of biochemical markers of bone turnover, bone alkaline phosphatase, osteocalcin, and Crosslaps, were significantly increased compared with the results obtained in young women, and significant negative correlations were found between these markers and hip bone mineral density. These results show that vitamin D status of a French aged population in good health and living at home depends mainly on lifestyle. Like institutionalized women, old women living at home exhibit clear evidence of senile hyperparathyroidism in the winter, secondary in part to a reduced 25OHD level and associated with biological signs of increased bone turnover. The maintenance of PTH within the normal range for healthy adults by vitamin D and calcium treatment might constitute an approach for the prevention of bone loss in the entire aged population.

Increased bone turnover in late postmenopausal women is a major determinant of osteoporosis.

Changes of bone turnover with aging are responsible for bone loss and play a major role in osteoporosis. Although an increase of bone turnover has been documented at the time of menopause, the subsequent abnormalities of bone resorption and formation and their potential role in determining bone mass in the elderly have not been investigated. To address this issue, we have measured a battery of new sensitive and specific markers of bone turnover in a population-based study of 653 healthy women analyzed cross-sectionally, including 432 women postmenopausal from 1 to 40 years, and the data were correlated with bone mineral density (BMD) measured by dual-energy X-ray absorptiometry (DXA) at different skeletal sites. Bone formation was assessed by serum osteocalcin (OC), serum bone-specific alkaline phosphatase (B-ALP), serum C-propeptide of type I collagen (PICP), and bone resorption by the urinary excretion of two pyridinoline cross-linked peptides (NTX and CTX). Bone turnover increased in perimenopausal women with both irregular menses and elevated serum follicle stimulating hormone (FSH). Menopause induced a 37-52% and 79-97% increase in the bone formation and bone resorption marker levels, respectively (p < 0.0001 except for PICP). In postmenopausal women, bone formation markers did not decrease with age. When resorption markers were corrected by whole body bone mineral content (BMC), the fraction of bone resorbed per day was not correlated with age in postmenopausal women and remained elevated for up to 40 years after menopause. In premenopausal women, the bone turnover rate accounted for only 0-10% of the variation in whole body BMC, total hip, distal radius, and lumbar spine BMD. With increasing time after menopause, the importance of the bone turnover rate as a determinant of bone mass increased at all sites and accounted for up to 52% of the BMD variance in elderly women. Thus, in women 20 years or more postmenopause, bone turnover was higher in those in the lowest quartile than in those in the highest quartile of BMD. In elderly women, 20 years since menopause and over, but not in younger ones, serum PTH was negatively correlated with serum 25-hydroxyvitamin D (r = -0.22, p < 0.05) and explained only 5-8% of the bone turnover variance (p < 0.01-0.001). These data indicate that the overall rates of both bone formation and bone resorption remain high in elderly women. The rate of bone turnover appears to play an increasing role as a determinant of bone mass with increasing time since menopause with a high bone turnover rate being associated with a low bone mass. Thus assessing bone marker levels may be useful in the evaluation of osteoporosis risk. In elderly women, secondary hyperparathyroidism caused in part by reduced serum 25-hydroxyvitamin D appears to be a marginal determinant of an increased bone turnover rate.

Biochemical effects of calcium and vitamin D supplementation in elderly, institutionalized, vitamin D-deficient patients.

Forty-five subjects (41 women and 4 men) in long-stay and medium-stay facilities, aged 74 to 95 years (mean 86.4 years), with 25-hydroxy-vitamin D levels less than 12 ng/ml, were treated for six consecutive months with two tablets per day of a preparation containing vitamin D3 (800 IU/day) and calcium carbonate (1 g elemental calcium/day). Serum levels of 25-hydroxy-vitamin D were very low at baseline (5.6 +/- 0.4 ng/ml) and rose significantly under treatment, to normal values, 33.2 +/- 1.2 and 40.9 +/- 2.1 ng/ml after three and six months, respectively (p < 0.001 for both comparisons). Serum calcium increased significantly, by 4.5% (p < 0.001) during the first three months, and remained at a plateau thereafter. Corrected serum calcium rose by 8.9% (p < 0.001) during the trial. No patient developed hypercalcemia. Serum parathyroid hormone levels, which were elevated at baseline (71.6 +/- 5.8 pg/ml; normal, 12 to 54 pg/ml), decreased gradually and significantly throughout the treatment period, by 43.0% and 67.1% after three and six months, respectively (p < 0.001 for both comparisons). Serum alkaline phosphatase activity fell concomitantly, by 9.9% after three months (p < 0.01) and 36.5% after six months (p < 0.001). In conclusion, the preparation used in our study is effective in correcting both the vitamin D deficiency that is prevalent in elderly institutionalized patients and the resultant increase in bone turnover.

Prevention and treatment of osteoporosis.

Because the lifetime risk of fragility fracture for a 50-year-old Caucasian woman is about 40 per cent, a whole-life strategy of osteoporosis prevention is necessary. In childhood, primary prevention of osteoporosis is based on exercise and adequate dietary calcium. In women undergoing menopause, hormone replacement therapy administered for at least ten years remains the preventive treatment of choice, and is associated with a substantial reduction in vertebral and non-vertebral fractures. Intranasal salmon calcitonin and bisphosphonates are effective alternatives, but their effects on fracture rate and their long-term safety require further evaluation. Regarding the prevention of the late bone loss leading to senile osteoporosis, there is now evidence that the reduction of the secondary hyperparathyroidism induced by calcium and vitamin D insufficiencies through the administration of calcium and vitamin D supplements significantly decreases the hip fracture incidence. There is no general consensus about the efficacy of treatment for established osteoporosis with fractures. Fluoride salts have proven their direct stimulating effects on bone formation; dosage must be moderate, and the duration of treatment should be limited to 2-3 years in order not to impair the quality of the new bone. Cyclical therapy with etidronate induces beneficial effects on bone mass in the spine, but its effect on the vertebral fracture rate is not yet established. The new bisphosphonates seem to be promising for the management of osteoporosis. Several other agents such as growth factors, silicon derivatives and strontium salts are in various stages of testing. The new definition of osteoporosis proposed by a WHO study group, no longer based on the fracture but on a low bone mass, is of major interest, because it should make possible to have a more effective therapeutic approach, before the occurrence of an irreversible degree of bone loss.

[Physiopathology and prevention of fractures of the proximal end of the femur]. / Physiopathologie et prévention des fractures de l'extrémité supérieure du fémur.

Hip fracture is the most important skeletal problem in elderly people. Its two main determinants are falls and bone loss leading to an intrinsic bone fragility. Bone fragility results from postmenopausal and senile bone loss. The latter is increased by the secondary hyperparathyroidism of elderly persons which is induced by a combination of vitamin D deficiency and calcium intake, both very common in old age, particularly in Europe. Prophylactic strategies should be based on prevention of falls and of bone fragility. The latter includes the optimization of peak bone mass during childhood, postmenopausal oestrogen replacement therapy and a late prevention of senile secondary hyperparathyroidism by vitamin D and calcium supplements which have recently been shown to reduce by 25% the number of hip fractures in a prospective study performed in a large population of institutionalized women. Therefore, it is never too early to pay attention to the risk of osteoporosis, and never too late to prevent hip fractures.

Serum undercarboxylated osteocalcin correlates with hip bone mineral density in elderly women.

We previously showed that circulating undercarboxylated osteocalcin (ucOC) is elevated in elderly women and is a powerful marker of the subsequent risk of hip fracture in elderly institutionalized women (J Clin Invest 1993; 91:1769). To investigate the relationship between bone mass and ucOC, we measured bone mineral density (BMD) of the hip with dual-energy x-ray absorptiometry in 98 elderly institutionalized women, 81.4 +/- 6.0 years old. ucOC was negatively correlated with BMD at all sites (r = -0.26 to -0.38, p < 0.001 to p < 0.0001), even after exclusion of the effect of age by partial correlation (for the femoral neck, r = -0.26, p < 0.01) and after controlling for serum parathyroid hormone. BMD was significantly lower at all sites of measurement in women with elevated ucOC (> 1.65 ng/ml, upper limit of the normal range in young women) than in those with normal ucOC (for the neck, 0.58 +/- 0.13 versus 0.43 +/- 0.13 g/cm2, p < 0.001). Similar results were obtained for ucOC expressed as the fraction of total OC (ucOC%). Multiple regression showed that ucOC has the highest predictive value for BMD when including age and body weight in the equation. In summary, our data indicate that serum ucOC is an independent determinant of BMD of the hip in elderly women. The mechanism by which serum ucOC is related to bone mass is unclear and should be addressed in further studies. However, our data suggest that ucOC level may be an interesting marker in the investigation of bone status in the elderly.

Ultrasound measurements on the os calcis in a prospective multicenter study.

Ultrasonic assessment is a new approach to assess both quality and density. Two ultrasonic parameters are measured on the os calcis: the attenuation or broadband ultrasound attenuation (BUA) and the velocity or speed of sound (SOS). The interunit variations in vitro and in vivo of an ultrasound instrument, the Lunar Achilles system, used in a French multicenter study named EPIDOS, were calculated and the stability of these instruments over a 12-month period was evaluated. A third parameter called "stiffness index," calculated from the SOS and BUA, was also used in this study. The average CV in vitro for the BUA and SOS was 0.92% and 0.12%, respectively, and the average CV in vivo for the BUA, the SOS, and the stiffness index was 1.83%, 0.23%, and 1.9%, respectively. The interunit (or inter-machines) variations were calculated by a one-way analysis of variance. We detected small but significant measurement differences among centers on a phantom for both SOS (maximum significant difference 0.4%) and stiffness (maximum significant difference 3.5%) but not for BUA. Similar differences were found in vivo. The precision over 12 months of the interunit variations in vitro was evaluated by measuring a single phantom traveling from one center to another several times. The range of the CV for the BUA (1.54-0.51%), for the SOS (0.25-0.14%), and for the stiffness index (2.26-1.10%) are explained in part by technical failures. The variation among the five Achilles was estimated by the combined CV which was 1.42% for the BUA, 0.32% for the SOS, and 2.33% for the stiffness index. In conclusion, our findings indicate that equipment from one manufacturer appears to be consistent between machines for the BUA, but not completely for the SOS. The results for this stiffness index are necessarily influenced by both SOS and BUA. The short-term and long-term interunit precision is good, both in vitro and in vivo. Such results provide increased confidence in multicenter clinical trials where ultrasonic data are pooled.

Can we stop bone loss and prevent hip fractures in the elderly?

The two main determinants of hip fractures are falls and bone loss leading to an intrinsic femoral fragility. Substantial femoral bone loss continues throughout old age, with a continuous and exponential increase in the risk of hip fracture; thus any reduction or arrest of this loss will induce an important reduction in the incidence of hip fracture. Preventive measures may be achieved during childhood by increasing peak bone mass with calcium and exercise, by using long-term estrogen replacement therapy after menopause, but also by using vitamin D and calcium supplements for late prevention in the elderly. Vitamin D insufficiency and a deficit in calcium intake are very common in the elderly living either in institutions or at home and the cumulative response to these deficits is a negative calcium balance which stimulates parathyroid hormone secretion. This senile secondary hyperparathyroidism is one of the determinants of femoral bone loss and can be reversed by calcium and vitamin D supplements. We have shown in a 3-year controlled prospective study that the daily use of supplements (1.2 g calcium and 800 IU vitamin D3) given in a large population of 3270 elderly ambulatory women living in nursing homes reduced the number of hip fractures by 23% (intention-to-treat analysis). In parallel, serum parathyroid hormone concentrations were reduced by 28% and low baseline serum 25-hydroxyvitamin D concentration returned to normal values. After 18 months of treatment the bone density of the total proximal femoral region had increased by 2.7% in the vitamin D3-calcium group and decreased by 4.6% in the placebo group (p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Relationship between bone fluoride content and histological evidence of calcification defects in osteoporotic women treated long term with sodium fluoride.

Fluoride treatment is used to increase bone formation and cancellous bone mass in patients suffering from postmenopausal osteoporosis with vertebral fractures. Patients submitted to similar therapeutic protocols have shown various histological responses to the treatment, some developing calcification defects and others not. In fact, the bone histological response to fluoride salts depends on the cumulative uptake of fluoride by bone. To clarify the relationship between the presence of calcification defects (identified by the presence of mottled bone and linear formation defects) and the bone fluoride content, a retrospective study was performed on 29 women with type 1 osteoporosis and treated for several months (11-24) with sodium fluoride (50 mg/day), calcium and vitamin D. Bone fluoride content always significantly increased after treatment, but it was significantly higher in patients showing calcification defects than in those having no defects. These differences between the two groups of patients were not due to differences in clinical details (no significant differences concerning age, duration of treatment, total amount of fluoride ingested, renal function) or in their bone remodelling activity. Thus, it may be hypothesized that the high bone fluoride uptake is due to different individual responses from one patient to another concerning the bioavailability of the same dose of fluoride. This is difficult to predict, except by testing the individual bioavailability of the compound to be used in each patient before starting long-term treatment.