EFFECT OF SLOW-RELEASE SODIUM-FLUORIDE ON CANCELLOUS BONE-HISTOLOGY AND CONNECTIVITY IN OSTEOPOROSIS

We have previously demonstrated that a treatment regimen of slow-relea se sodium fluoride (SRNaF) and continuous calcium citrate increases lu mbar bone mass, improves cancel lous bone material quality, and signif icantly reduces vertebral fracture rate in osteoporotic patients. In o rder to assess whether such treatment also improves trabecular structu re, we quantitated cancellous bone connectivity before and following 2 years of therapy with SRNaF in 23 patients with osteoporosis and vert ebral fractures. In addition, we performed bone histomorphometry on th e same sections used for connectivity measurements. There was a signif icant increase in L2-L4 bone mineral density during therapy (0.827+/-0 .176 g/cm(2) SD to 0.872 +/- 0.166, p = 0.0004). Significant histomorp hometric changes were represented by increases in mineral apposition r ate (0.6+/-0.4 mu m/d to 1.1+/-0.7, p = 0.0078) and adjusted appositio n rate (0.4+/-0.3 mu m/d to 0.6+/-0.4, p = 0.016). On the other hand, trabecular spacing significantly declined (from 1375+/-878 mu m to 105 2+/-541, p = 0.05). Two-dimensional quantitation of trabecular struts on iliac crest histological sections disclosed significant increases i n mean node number per mm(2) of cancellous tissue area (0.22+/-0.12 vs . 0.39+/-0.27, p = 0.0077), the mean node to free-end ratio (0.23+/-0. 21 vs. 0.41+/-0.46, p < 0.05), and in the mean node to node strut leng th per mm(2) of cancellous area (0.098+/-0.101 vs. 0.212+/-0.183, p < 0.,01). There were no significant changes in any of the measurements a ssociated with free-end number or free-end to free-end strut length. W hen patients were divided into those with severe and mild-modest spina l bone loss (based upon initial lumbar bone density) the significant c hanges in connectivity occurred in patients with mild-moderate bone lo ss, but not in those with severe bone loss, suggesting that fluoride's effect is in part dependent on the presence of a certain critical amo unt of bone. This finding in combination with the previously reported increases in bone mass and bone material quality may explain the signi ficant reduction in vertebral fracture rate observed with this particu lar fluoride regimen.