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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.

Histomorphometric analysis of undecalcified sections was performed in transiliac biopsy cores taken from 29 patients (16 men, 13 women, aged 51 ± 17 years) suffering from skeletal fluorosis due to chronic exposure to fluoride. The origin of the exposure, known in 20 patients, was either hydric (endemic or sporadic), or industrial, or in a few cases iatrogenic. Measured on calcined bone using a specific ion electrode, bone fluoride content was significantly high in each specimen (mean ± SD: 0.79 ± 0.36% of bone ash) as compared to control values (< 0.10%). The radiologically evident osteosclerosis observed in each patient was confirmed by the significant increase of cancellous bone volume (40.1 ± 11.2 vs. 19.0 ± 2.8% in controls, p< 0.0001). There were significant increases in cortical width (1292 ± 395 vs. 934 ± 173 μm, p< 0.0001) and porosity (14.4 ± 6.4 vs. 6.5 ± 1.7%, p< 0.002), but without reduction of cortical bone mass. Osteoid parameters were significantly increased in fluorotic patients. The increase in cancellous osteoid perimeter was almost threefold greater than that noted in cancellous eroded perimeter. The fluorotic group had a greater number of osteoblasts than controls, with a very high proportion of flat osteoblasts. In 15 patients doubly labeled with tetracycline, the mineral apposition rate was significantly decreased, while mineralization lag time significantly increased. Bone formation rate and adjusted apposition rate were significantly decreased in skeletal fluorosis. Cancellous wall width was normal in fluorosis but the formation period and active formation period were significantly increased. Skeletal fluorosis is thus characterized by an unbalanced coupling in favor of bone formation, and also by a great number of osteoblasts with a high proportion of flat osteoblasts. These osteoblasts have a very increased formation period mainly due to a prolonged inactive formation period. Our results support the view that fluoride may have a dual effect on osteoblasts: an increased birthrate at the tissue level, and a toxic effect at the individual cell level. The addition of these two effects represents, however, a marked increase of bone formation at the organ level.