TEACHING EDITORIAL

New Evidencefor Sodium Fluoride in Osteoporosis

There are few problems in clinical medicine more frustrating than the traumatic fracture asso ciated with the multiple causes of osteoporosis. The osteoporosis of the spinal crush fracture syn drome is a traditional hallmark of this dilemma. We know only too well that adult bone loss and its sequelae are the greatest challenge to health and longevity, exceeding cardiovascular-renal dis ease and cancer in prevalence. As Garn (1 ) pointed out, “ifwe live long enough, we all experience forearm fractures, or fractures of the femoral neck and trochanteric region, and incur a $10,000 charge for surgery, hospital, and nursing care―(in 1980). How many ofour future backaches will stem from osteoporosis and its consequences, as shown in Fig. I ? Fractures of the distal radius (Colles's fractures) increase in frequency in women past 50 and are at least as common as corn pression fractures. Since they are more easily cared for, they are less of a problem than the chroni cally recurring and incapacitating vertebral compression fractures. Sodium fluoride (NaF) is the only agent available that will stimulate bone formation rate (2). At the present time, however, it has not been cleared by the FDA for the treatment of osteoporosis. Two double-blind studies, both funded by NIH, are in progress, one at the Mayo Clinic and the other at Henry Ford Hospital, each designed to evaluate the effectiveness of NaF for the treat ment of postmenopausal osteoporosis. The effects of calcium and NaF are being compared with the effects of calcium alone. It is anticipated that the results of these studies will provide definitive information in this regard. If efficacy of NaF is confirmed, there should be a substantial increase in its use for treatment ofosteoporosis. Estrogen may increase bone mass minimally, but estrogens and calcium and vitamin D probably owe most of their effect in reducing vertebral fractures to the ability of these agents to arrest or retard the rate of bone loss. Even with fluorides, it is likely that at least 1 year of treatment would be required to increase bone mass substantially. In the series of Riggs et al. (3), 60% of the patients treated with NaF had radiologically apparent increases in ver tebral bone mass. Patients with these changes had only “-‘1/7of the vertebral fracture rate of the rest of their patients with postmenopausal osteoporosis. Even so, there is a substantial minority of patients (perhaps 40%) who do not respond to years of treatment. Sodium fluoride may serve as a probe to identify this important subgroup of patients among those in whom impaired osteoblastic activity contributes to the pathogenesis. A deceleration of bone resorption or an improvement in mineralization is probably more asses sable by gamma imaging than by any currently available imaging technique (4). Because of the greater regional variability in bone disease, measurement of the total skeleton may be more useful diagnostically. Corticosteroids, for example, preferentially predispose to spinal osteopenia. Use of local measurements in appendicular bones would misrepresent actual bone changes by a factor of five or ten in such cases (5). Previously, there has been no clinically useful noninvasive means to evaluate the effects of NaF on the peripheralskeleton.In the presentissueof theJournal, Dr. Schulzandhiscolleagues(6) report the novel use of Tc-99 methylene diphosphonate to evaluate the skeletal response to NaF. The method not onlyallowsa degree of quantification of enhanced activity but, importantly, also delineates the sites at which the increases in bone formation occur. Increases in total and skeletal alkaline phosphatase activity provide additional evidence for enhanced bone-formation rate. The development of bone pain in five patients in an affected region—one that was normal by conven tional radiographs—is additional evidence for the sensitivity of this technique. Only discontinuing NaF therapy reduced the pain immediately and gave complete relief of the rheumatic syndrome in 2-3 wk. Although the patients complain ofjoint pain, the bone scintigram suggests a metaphy seal periostitis. This is reminiscent of the change seen in pulmonary osteoarthropathy, when pain is manifested in the joints but the image changes stop at the metaphysis. The posttherapy images show changes much earlier than can be expected by bone roentgenographic studies, and the action

720 TIlE JOURNAL OF NUCLEAR MEDICINE TEACHING EDITORIAL

AGE 60 65 75

FIG. 1. lllustratin9 osteoporosis of spine and its consequences. Each set of frac ttres causespain,deformfty,andreduction inheight.

of NaF on peripheral (appendicular) bone. Previous work with single-photon absorptiometry of the distal radius did not demonstrate this effect. One question raised by the studies is why such variation occurs in sites of increased activity in response to NaF. A more symmetrical pattern of distribution would have been anticipated. The treatment of osteoporosis by NaF can be evaluated in an ongoing sequence as follows: First: evidence of increased osteoblastic activity by pre- and posttherapy bone scintigram at 4 to 8 mo; Second: evidence of increased bone mass by bone density measurements at I—2yr; Third: evidence that the above changes have resulted in a decreased number of osteoporotic fractures over a 10-yr period. The authors of the current article (6) point out that the bone scintigram is a useful tool for eval uating industrial and endemic fluoride exposure. This is an obvious suggestion to the National In stitute of Occupational Safety and Health for workers exposed to fluoride. This group has previ ously advised radiographic screening before employment and every 6 years thereafter. If this is such an obvious use of bone scintigraphy, why wasn't it used earlier? Perhaps because bone images do not quantify the mass. Just as muscle mass usually correlates with strength, so does bone mass. Bone images quantify osteoblastic activity. This activity leads to bone growth, as in a reaction to injury, but it does not precisely answer the problem of mass. My enthusiastic sup port of bone scintigraphy has to do with physiology, not pathology; functional repair, not structure. It will be necessary to require noninvasive measurements of local bone mass and structure in osteo porosis. JOHNSELBY,SR VA Medical Center Charleston, South Carolina

ACKNOWLEDGMENTS

The author thanks Dr. Norman Bell for his valuable discussion of this manuscript. He also acknowledges with appreciation the artistic assistance of Mrs. Karen Temple and the editing and typing of Mrs. Dorothy Beecham.

Volume 25, Number 6 721 TEACHING EDITORIAL

REFERENCES

I. GARN SM: The phenomenon of bone formation and bone loss. In Osteoporosis, Recent Advances in Pathogen. esis and Treatment. DeLuca HF, Frost HM, Jee WSS, et al, eds. Baltimore, University Park Press, pp 3-16, I981 2. JOWSEY J, RIGGS BL, KELLY PJ, et al: Effect ofcombined therapy with sodium fluoride, vitamin D and calci um in osteoporosis. Am J Med 53:43-49, 1972 3. RIGGS BL, SEEMAN E, HODGSON SF, et al: Effect of the fluoride/calcium regimen on vertebral fracture oc currence in postmenopausal osteoporosis. N Engl J Med 306:446-450, 1982 4. SY WM: Osteoporosis. In Gamma Images in Benign and Metabolic Bone Disease. Vol I. Sy WM, ed. Boca Raton, FL, CRC Press, 1981, pp 223-239 5. MAZESS RB: Noninvasive measurement of local bone in osteoporosis.In Osteoporosis, Recent Advances in Pathogenesis and Treatment. DeLuca H F, Frost HM, Jee WSS, et al, eds. Baltimore, University Park Press, 1981, pp 25-36 6. SCHULZ EE, LIBANATI CR, FARLEY SM: Skeletal scintigraphic changes in osteoporosis treated with sodium fluoride. J Nucl Med 25:65 1-655, 1984

722 THE JOURNAL OF NUCLEAR MEDICINE