Bone remodeling and calcium metabolism: a correlated histomorphometric, calcium kinetic, and biochemical study in patients with osteoporosis and Paget's Disease.

The extent to which histomorphometric analysis of bone biopsies correlates with Ca kinetic and biochemical parameters to reflect true bone formation and resorption in adult man remains an unsolved issue. Two groups of patients with either low (osteoporosis), (n = 15) or high (Paget's disease, n = 6) bone turnover were studied before and after sodium fluoride (NaF) and diphosphonate (EHDP) treatment, respectively. Histomorphometry of iliac crest biopsies permitted precise quantitation of the osteoblast layers (SVab), osteoid seams (SVos), the number of osteoclasts (NAocl) and the Howship's lacunae (SVhl). These determinations were correlated with serum alkaline phosphatase (aPh), urinary hydroxyproline (HyPro), Ca accretion rate (Vo+), and Ca mobilization rate (Vo-). In both patient groups bone formation indices were significantly correlated: SVob/Vo+, r = 0.85; SVos/Vo+, r = 0.83; and aPh/Vo+, r = 0.97. Provided that bone matrix formation and mineralization progess at the same rate, bone formation may be assessed by measuring either aPh, Vo+, SVob, or SVos. From these correlations it is not possible to draw any conclusions regarding the absolute "true" value of bone formation, be it in terms of Ca kinetics, alkaline phosphatase, or histomorphometry. However, since Vo+ retains its proportionality to all the other bone formation parameters tested, the so-called "slow exchange," which refers to pure physicochemical Ca exchange processes in the bone mineral, does not perturb Vo+ in an unsystematic way. Vo+ as well as aPh and histomorphometric indices are thus reliable, though not absolute indices of bone formation. Bone resorption indices correlated less well than bone formation indices: NAocl/Vo-, r = 0.68 and SVhl/Vo-, r = 0.63 with both groups. In the osteoporotic group, a negative correlation existed between the empty Howship's lacunae SVhe and Vo+, r = -0.62. Consequently, the overall extent of Howship's lacunae SVhl is influenced both by bone resorption and bone formation. On the other hand, the best correlation of HyPro was with the sum of Vo+ and Vo-, r = 0.97, confirming that HyPro is a sensitive index for the change of bone turnover.