Cm. Schnitzler et al., FEWER BONE HISTOMORPHOMETRIC ABNORMALITIES WITH INTERMITTENT THAN WITH CONTINUOUS SLOW-RELEASE SODIUM-FLUORIDE THERAPY, Osteoporosis international, 7(4), 1997, pp. 376-389
To help resolve the uncertainty whether sodium fluoride (NaF) therapy
should be given intermittently or continuously, we examined iliac cres
t bone biopsies (before and after treatment) and fragility fracture ra
tes in 35 intermittently treated (group I) and 69 continuously treated
(group C) patients; all received calcium. The following statistically
significant results were obtained, Reduction in vertebral fracture ra
te was similar in the two groups. Trabecular thickness and the structu
rally more important mineralized thickness increased only in group I.
Group I also accumulated less excess osteoid (surface, volume). Mean o
steoid thickness did not change in either group because of a bimodal d
istribution of wide seams with osteoblasts and double tetracycline lab
els, and thin seams without osteoblasts or labels. Osteoid was lamella
r. Osteoid in abnormal sites (within bone marrow or bone, or around os
teocytes) was found less frequently in group I. Adjusted apposition ra
te declined and mineralization lag time increased in both groups becau
se of extended unlabelled osteoid seams. Erosion surface increased onl
y in group C. Hook and/or tunnel erosion was seen less frequently in g
roup I; it was closely associated with osteoid in abnormal sites and c
orrelated with osteoid surface. Extended osteoid surface may have forc
ed osteoclasts to hollow out trabeculae, leaving the empty osteoid she
ll in marrow. Excess osteoid volume and eroded surface and osteoid and
erosion in abnormal sites correlated with bone fragility in group C.
We conclude that intermittent therapy is to be preferred because it (1
) increased mineralized trabecular thickness, (2) did not cause excess
ive osteoid accumulation and erosion, (3) showed less osteoid and eros
ion in abnormal sites and (4) led to a similar reduction in the verteb
ral fracture rate as did continuous treatment. The question of whether
intermittency of therapy has some other effect independent of the cum
ulative dose of fluoride administered cannot be answered by this study
.