Applied Radiology

PROBLEM:

Four different patients with the same condition have undergone conventional radiographic evaluation. What is the most likely diagnosis?

ANSWER:

Vitamin D therapy for rickets in childhood.

DISCUSSION:

Rachitic and osteomalacic syndromes display remarkably similar histologic and radiological features regardless of etiology, making a specific diagnosis difficult from radiographs alone. A few of the rachitic and osteomalacic syndromes may have characteristic radiological findings that permit a more precise diagnosis.

General radiological features (figures 1 to 4)-Changes of rickets occur at open growth plates and are best seen in those areas showing most active growth. The growth plate shows axial and latitudinal widening. The trabecular bone subjacent to the growth plate is de-mineralized and disorganized.1,2 Changes of osteomalacia may be identified in the already mature areas of the skeleton. The deformities caused by rickets exhibit different patterns, depending on the age of the child when the disease develops; such deformities are related to posture and activity.3,4,15 The diagnosis of the specific disease entity requires correlation of the radiographs with clinical history and laboratory data. Infection in the newborn, such as rubella, can present irregularities of the physis region. Trauma sometimes may produce widening of growth plate areas, but the changes are not generalized.

The diagnosis of osteomalacia is difficult. In addition to generalized osteopenia, areas of spongy bone may show a decrease in the total number of trabeculations owing to a loss of secondary trabeculae. The remaining trabeculae appear prominent and project a "coarsened" pattern; their margins may reveal an unsharpness reflecting the inadequately mineralized surface matrix (osteoid borders or seams). Lucent areas in the cortex indicate irregular haversian canals, which appear widened due to surface accumulations of osteoid.

Osteoid may be deposited in excessive amounts at various sites, particularly in the spine and pelvis. Although this osteoid remains relatively mineral deficient per unit area, the excessive quantity of osteoid can result in increased radiodensity. This is particularly true in renal osteodystrophy.

Pseudofractures, or Looser's zones, may precede other radiographic changes of osteomalacia.21 These linear radiolucencies are oriented at right angles to the cortex and incompletely span the diameter of the bone. Pseudofractures commonly are symmetric and occur in characteristic sites, such as the superior and inferior pubic rami, ribs, axillary margins of the scapula, inner margins of the proximal femurs, and posterior margins of the proximal ulna. Sclerosis often demarcates the margins. New bone on the periosteal aspects suggests callus formation, and true fractures can occur through these weakened areas. Pseudofractures occur at sites of stress having a high bone turnover. Histologically, pseudofractures consist of unmineralized osteoid deposited during the repair process.

The general radiological features described previously are shared (at least in part) by all of the various rachitic and osteomalacic syndromes. When confronted with these nonspecific radiological changes, the diagnostic considerations may be etiologically organized. The following points also may be helpful. In rachitic patients less than 6 months of age, consider neonatal rickets, biliary atresia, vitamin D-dependent rickets, and hypophosphatasia. If there is "resistance" to usual therapeutic doses of vitamin D (in the absence of chronic glomerular renal disease), consider a renal tubular disorder, tumor, hypophosphatasia, or metaphyseal chondrodysplasia, Schmid-type.Syndromes that may have characteristic radiological findings in addition to the general features of rickets or osteomalacia:

1. Renal osteodystrophy (uremic osteopathy)-Radiological changes of secondary hyperparathyroidism usually are present and frequently are prominent. Osteosclerotic foci in trabecular rich bone, particularly adjacent to the end plates of the vertebral bodies ("rugger-jersey spine"), are characteristic. Vascular calcification of the Mönckeberg type and, less commonly, large deposits ("tumoral") of amorphus calcification may be identified, particularly around joints.

2. X-linked hypophosphatemia-In children, rachitic changes at the growth plates often are only moderate or mild in degree. Osteopenia may not be prominent; in fact, the bones often are "strong" in appearance. Bowing of long bones, particularly of the lower extremities, may occur, but deformity frequently is minimal, and the condition may be overlooked in childhood. With increasing age, the trabecular pattern becomes coarsened. By adulthood, a generalized increase in bone density, especially in the axial skeleton, is characteristic.16,20

In addition to increased vertebral body density, calcification in the paravertebral ligaments, annulus fibrosus, and capsules of apophyseal joints may develop. The changes superficially resemble those of idiopathic ankylosing spondylitis.16 In the pelvis, sites of calcification may involve the acetabulum, iliolumbar ligaments, and sacroiliac joints. The appendicular skeleton shows multiple sites of new bone formation at various muscle and ligamentous attachments. Separate small ossicles may develop around various joints, particularly the carpus.2,16

3. Atypical axial osteomalacia-Radiological abnormalities of osteomalacia are confined to the lumbar spine, pelvis, and ribs. The cervical spine may show a dense, coarse trabecular pattern. The skull is normal. Looser's zones have not been identified.3,6

4. Hypophosphatasia-Radiological changes vary

in severity. Newborns may show advanced demineralization. Rachitic growth plates show characteristic multiple radiolucent extensions into the metaphysis. Wormian bones and craniosynostosis may be present.

5. Metaphyseal chondrodysplasia, Schmid-type-Multiple small bony projections extend from the metaphysis into the widened growth plates. Long bones maintain normal density. Spontaneous improvement occurs.5,7-14,17-19,22-25

References

1. Bloom WL, Flinchum D: Osteomalacia with pseudofractures caused by ingestion of aluminum hydroxide. JAMA 174:181-184, 1960.

2. Coburn JW, Brickman AS, Hartenbower DL: Clinical disorders of calcium metabolism in relation to vitamin D. In: Vitamin D and Problems Related to Uremic Bone Disease. Proceedings of the Second Workshop on Vitamin D, Wiesbaden, West Germany, October 1974, pp 219-240. New York, Walter de Gruyter, 1975.

3. Condon JR, Nassim JR: Axial osteomalacia. Postgrad Med J 47:817-820, 1971.

4. DeLuca HF: The kidney as an endocrine organ for the production of 1,25-dihydroxyvitamin D3, a calcium-mobilizing hormone. N Engl J Med 289:359-365, 1973.

5. DeLuca HF: The kidney as an endocrine organ involved in the function of vitamin D. Am J Med 58:39-47, 1975.

6. Frame B, Frost H, Ormond R, et al: Atypical osteomalacia involving the axial skeleton. Ann Intern Med 55:632-639, 1961.

7. Haussler M, Hughes M, Baylink D, et al: Influence of phosphate depletion on the biosynthesis and circulating level of 1,25-dihydroxyvitamin D. Advances Exp Med Biol 81:233-250, 1977.

8. Holick MF, McNeill SC, MacLaughlin JA, et al: Physiologic implications of the formation of previtamin D3 in skin. Trans Assoc Am Phys 92:54-63, 1979.

9. Holick MF, Uskokovic M, Henley JW, et al: The photoproduction of 1,25-dihydroxyvitamin D3 in skin. An approach to the therapy of vitamin-D-resistant syndromes. N Engl J Med 303:349-354, 1980.

10. Kanis JA, Cundy T, Bartlett M, et al: Is 24,25-dihydroxycholecalciferol a calcium-regulating hormone in man? Br Med J 1:1382, 1978.

11. Kream BE, Jose M, Yamada S, et al: A specific high-affinity binding macromolecule for 1,25-dihydroxyvitamin D3 in fetal bone. Science 197:1086-1088, 1977.

12. MacLennan WJ, Hamilton JC: Vitamin D supplements and 25-hydroxy vitamin D concentrations in the elderly. Br Med J 2:859-861, 1977.

13. Manolagas SC, Taylor CM, Anderson DC: Highly specific binding of 1,25-dihydroxycholecalciferol in bone cytosol. J Endocrinol 80:35-39, 1979.

14. Ornoy A, Goodwin D, Noff D, et al: 24,25-dihydroxyvitamin D is a metabolite of vitamin D essential for bone formation. Nature 276:517, 1978.

15. Park EA: The Blackader lecture on some aspects of rickets. Can Med Assoc J 26:3-15, 1932.

16. Patton JT: Skeletal changes in hypophosphataemic osteomalacia, p 229. Symposium Ossium. London, E & S Livingstone Ltd, 1970.

17. Pierides AM, Ellis HA, Kerr DNS: Phosphate-deficiency osteomalacia during regular haemodialysis. Lancet 2:746, 1976.

18. Pitt MJ, Haussler MR: Vitamin D: Biochemistry and clinical applications. Skel Radiol 1:191-208, 1977.

19. Rasmussen H, Bordier P, Kurokawa K, et al: Hormonal control of skeletal and mineral homeostasis. Am J Med 56:751-758, 1974.

20. Steinbach HL, Kolb FO, Crane JT: Unusual roentgen manifestations of osteomalacia. AJR 82:875-886, 1959.

21. Steinbach HL, Noetzli M: Roentgen appearance of the skeleton in osteomalacia and rickets. AJR 91:955-972, 1964.

22. Szymendera J, Galus K: Effect of 24,25-dihydroxycholecalciferol on calcium absorption in proximal small intestine in uraemia. Br Med J 2:1465-1466, 1978.

23. Tanaka Y, DeLuca HF: Role of 1,25-dihydroxyvitamin D3 in maintaining serum phosphorus and curing rickets. Proc Natl Acad Sci 71:1040-1044, 1974.

24. Weber JC, Pons V, Kodicek E: The localization of 1,25-dihydroxycholecalciferol in bone cell nuclei of rachitic chicks. Biochem J 125:147-153, 1971.

25. Weisman Y, Salama R, Harell A, et al: Serum 24,25-dihydroxyvitamin D concentrations in femoral neck fracture. Br Med J 2:1196-1197, 1978.