Regional migratory osteoporosis of the lower extremities with vertebral osteoporosis

Bone, 7, 343-349 (1986) Printed in the USA. All rights reserved.

8756-3282186 $3.00 + .OO Copyright 0 1986 Pergamon Journals Ltd.

Regional Migratory Osteoporosis of the Lower Extremities with Vertebral Osteoporosis V. MAVICHAK,’ T.M. MURRAY,* A.B. HODSMAN, N.J. ROBERT,4 and R.A.L. SUTTON’

1 Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada 2 Unwerwty of Toronto, Ontario, Canada. 3 University of Western Ontario, London, Ontario, Canada. 4 Tufts Univers/ty, Boston, Massachusetts, USA.

Address for correspondence and reprints:: Dr. R.A.L. Sutton, Department of Medicine, 910 West 10th Avenue, Vancouver, B.C. V5Z 1 M9 Canada.

Abstract

Regional migratory osteoporosis is a disorder of un- known etiology, characterized by successive episodes of joint pain, accompanied by localized osteoporosis. The disorder affects the lower limbs, usually the region of the foot, knee, or hip, and each episode usually lasts several months and is followed by spontaneous recovery. This disorder has not previously been reported to cause episodes of vertebral osteoporosis, We describe three patients in whom regional osteoporosis, involving the lower limbs, was associated with simultaneous vertebral osteoporosis indistinguishable from idiopathic osteoporosis. These cases suggest that this disorder might be responsible for some cases of apparent idiopathic spinal osteoporosis.

Key Words: Migratory Osteoporosis-Osteolysis-Verte- brat Osteoporosis-Algodystrophy.

introduction

Regional migratory osteoporosis is a transient form of osteoporosis, which is characterized by local pain, swelling, and erythema involving the lower extremities. (Duncan et al., 1967, 1972; Sweezey, 1970; O’Mara and Pinals, 1970; Steiner and McKeever, 1973; Gupta et al., 1973; Langloh et al., 1973; Levy and Hinterbuckner, 1976; McCord et al., 1978; Resnick and Niwayama, 1981). Each episode de- velops spontaneously and rapidly, may last for several months, and later diminishes and disappears. Subsequent episodes occur in other regions of the same or the opposite lower extremity. Occasionally, more than one region may be involved at the same time, or episodes may overlap. Although multiple attacks are the usual feature of this syndrome, it has been claimed that attacks never recur in regions that were previously involved (Strashun and Chayes, 1979; Bray et al., 1979; Tannenbaum et al., 1980). Radiographic evidence of osteoporosis becomes apparent within weeks or months of the onset of symptoms, but it subsequently improves, with remineralization. Bone scanning reveals increased uptake of radio- activity in involved areas and is often useful in making the

diagnosis of this syndrome before radiographic signs of osteopenia appear (Duncan et al., 1972; Strashun and Chayes, 1979; Bray et al., 1979; Tannenbaum et al., 1980). The unique features of regional migratory osteoporosis involving the lower extremities have been recognized, but the association of vertebral osteoporosis with transient appendicular osteolysis has not been reported previously in the literature.

We describe three cases of regional migratory osteoporosis associated with simultaneous vertebral osteoporosis indistinguishable from idiopathic osteoporosis. These cases suggest that this disorder may be responsible for some cases of apparent idiopathic spinal osteoporosis.

Case Histories

Case 1

This 58-year-old man developed weightbearing pain in his right knee following minor trauma in 1973. The pain was associated with localized swelling, erythema, and warmth, which persisted for 1 year. In December 1974 he developed persistent low back pain, which lasted 21 months. X-rays taken in March 1975 (Fig. 1) showed lumbar spinal osteoporosis with compression fractures of Ll, L2, and L5, regional osteoporosis of the right knee (Fig. 2a) and a normal left knee (Fig. 2b). No previous spinal x-rays are available. Bone scanning revealed increased uptake involving Ll , L2, and L5 and slightly increased activity in the right knee and left upper femur (Fig. 3s).

As shown in Table I, all laboratory data were normal except for an elevated serum alkaline phosphatase of 229 IU/I (normal 30-85 lU/I). Bone marrow biopsy was normal. Bone biopsy of the left greater trochanter and right femoral condyle showed only evidence of osteoporosis without evidence of osteomalacia or acute or chronic inflammation in the bone. In November 1975, at which time low back pain was still present, the patient spontaneously developed weightbearing pain and swelling of the right foot, which lasted for 10 months. Diabetes mellitus was discovered at the same time and was treated with oral chlorpropamide. Except for an elevation of serum alkaline phosphatase (207 IU/I), all other laboratory tests, including urinary hydroxyproline, were normal.

343

344

Fig. 1. Case 1. Lateral radiograph of lumbar spine showing compression fractures of Ll, L2, and L5 vertebrae (March 1975)

V Mavlchak et al Migratory osteoporosis involving the vertebrae

X-ray of the spine was unchanged; regional osteoporosis was present In the right ankle, and despite the absence of pain in the knees, x-rays now showed spotty demineralization in both knees, more marked on the right. Bone scanning revealed an improvement of the lumbar sprne. a markedly increased uptake in the right foot, and slightly increased uptake in the left knee (Fig. 3b). In Sep- tember 1976, the patient developed chronic diarrhea and steatorrhea; a diagnosis of pancreatic insufficiency due to chronic pancreatitis was made. A repeat bone scan was normal. Occasional mild low back pain persisted until Au- gust 1978. There was no recurrence of pain In the lower extremities from September 1976 until the patient died of a myocardial infarction in 1980, and no further bone x-rays were taken. In summary, this 58-year-old man had regional migratory osteoporosis involving the right knee, lumbar spine, and right foot with spontaneous clinical recovery over the subsequent 2 years.

Case 2

This 43.year-old nurse had difficulties with her legs during her first pregnancy at about 18 weeks gestation in July 1980. Inrtially, her feet began to swell, especially when she worked a full shift. At about 24 weeks gestation, she began to experience severe pain in the right hip, which limited her walking. The pain was noted on weightbearing and was not related to joint movement. She required a cane for walking. Two weeks later she started to have weightbearing pain in her right knee as well, without swelling or erythema. By 28 weeks, her hip had become pain-free, but pain continued in the right knee. At about 33 weeks, she fell and subsequently suffered from muscle spasms and

Fig. 2. Case 1 a (left). Radiograph of right knee showing spotty osteoporosis of drstal femur and patella (March 1975) b (nght) Radiograph of normal left knee for comparison with right knee (March 1975)

V. Mavichak et al.: Migratory osteoporosis involving the vertebrae 345

Fig. 3. Case 1. Bone scans. a (left). March 1975 Shows increased uptake in Ll, L2, and L5 vertebrae and slight increase in left upper femur and right knee. b (right). November 1975. Shows disappearance of previous abnormalities in lumbar spine, a marked increase in uptake in the right foot, and a slight increase in the left knee.

marked tenderness of the upper end of the right fibula and right knee.

X-rays taken at this time showed localized osteoporosis around the right knee. She was unable to walk for a week, but the pain in her right knee disappeared after a week of bedrest. She was then able to walk with a walker. At 35 weeks, she developed bone pain in the right foot and ankle and, to a lesser degree, in the left foot. She delivered a normal infant by caesarean section at 41 weeks gestation. X-rays taken after delivery showed osteopenia around

her right knee and even more severe osteopenia in the right foot, particularly the calcaneum (Fig. 4a). Slight vertebral osteopenia was noted at this time radiologically. Laboratory data were normal, except for an elevated alkaline phosphatase (123 IU/I, normal 7-74 IU/I), which grad- ually fell to normal (67 IU/I) by October 1981.

She continued to have foot pain without swelling or erythema and needed a walker for 2 months following delivery. The foot pain persisted for 7 months, but she was pain-free by July 1981. In October 1981 she experienced some pain in the region of her upper dorsal spine when she carried her baby. By January 1982 she was again pain-free. On physical examination there was a mild sco- liosls convex to the right in the dorsal spine. Neurological examination was normal, with the exception of some re- sidual weakness of dorsiflexion of the feet, particularly on the right, and minimal weakness on hip flexion. Laboratory data were normal (Table I). X-ray revealed scoliosis, and generalized vertebral osteopenia with a small wedge compression of D8. Marked localized osteoporosis was also noted at the proximal end of both tibias and in the bones of the feet. Bone scanning was normal. Spinal bone density by neutron activation showed 63% of the predicted value (Harrison et al., 1979). A bone biopsy of the posterior iliac crest showed relatively low trabecular volume with evidence of low bone turnover but no evidence of osteomalacia.

Subsequently the patient has been asymptomatic. Ra- diological improvement was noted when the radiographs of the feet and ankles taken in January 1982 (Fig. 4b) and September 1983 were compared with those taken in De- cember 1980. In summary, this 43-year-old woman suffered from regional migratory osteoporosis involving right hip, right knee, both feet, and dorsal spine over a period of 2 years, with spontaneous recovery of the problems in her lower extremities. Spinal osteopenia, however, persists. Neutron activation analysis in June 1984 showed her spinal bone mass to be only 53% of predicted (Harrison et al., 1979).

Case 3

This 37-year-old woman developed left ankle pain following strenuous gardening in March 1978. The pain was associated with swelling, but no erythema was noted. In October 1980, she had severe pain in the left hip and lower rlorsal spine. X-ray revealed osteolysis involving cortical and trabecular bone at the ends of both tibias (Fig. 5), femora, radii, and humeri. There was also generalized osteopenia of the axial skeleton with a partial com-

Table I. Laboratory data from reported patients

Parameter

Serum Calcium mgldl

Serum inorganic phosphate

(mg/dl) Serum alkaline phosphatase

W/I Serum PTH

ngiml 24-h urinary

calcium (mg) 24-h urinary total

hydroxyproline (mg)

Case 1 March 1975

a.7

3.2 185

(normal 30-55) Not done

140-270 Normal

Case 2 January 1981

9.4

3.7 123

(normal 7-74) Not

detectable

Not done Noi done

Case 3 March 1981

9.7

3.4 86

(normal 25-120) 0.2

(normal)

88-174 23.5

(normal 6-22)

346 V Mavrchak et al Migratory osteoporosrs involving the vertebrae

Fig. 4. Case 2. a (left). Radiograph of right foot, December 1980, showing marked demineralization, especially of calcaneum. b (right) Radiograph of right foot, January 1982, showing striking remineralization In comparison with December 1980

pression fracture of T12 In March 1981 she developed weightbearing pain in her right ankle that was so severe that she required a crutch for walking. A bone scan revealed increased uptake involving both feet (Fig. 6a) but also in other areas, including 1st 5th, and 8th ribs on the left, T12 vertebra, right sacroiliac joint, right anterior iliac spine, and the left femoral head. Detailed metabolic rnves- tigation at this time revealed no biochemical abnormalities (Table I). An iliac crest bone biopsy with tetracycline la- beling showed severe trabecular osteopenia with low turnover and modestly impaired osteoblast function, but no evidence of osteomalacia. Subsequently there was some improvement in the ankle pain.

After the patrent developed acute lower dorsal back pain in August 1981, further x-rays showed a new compression fracture at T9 (Fig. 7). Another bone scan showed evidence of progression with increased uptake in the right second and left fourth ribs, and C2, C8. T4, T5, T9, and TIO vertebrae, in addition to the vertebral fractures

Fig. 5. Case 3. Radiograph of both ankles, October 1980, showing spotty demineralization of both lower tlb1a.s and fibulas

demonstrable by x-ray. In November 1981, she had a recurrence of acute pain in her right foot; x-rays showed evidence of a healing fracture in the proximal phalanx of the 4th left toe as well as a new fracture in the distal shaft of the rrght 2nd metatarsal bone Although repeat bone scannrng showed a definite improvement in the previous lesions, a new increase in uptake was noted at the right ankle (Fig. 6b). The patient was essentially pain-free until March 1982, when she had pain in both knees. Bone scanning showed continuing resolution of previous le- srons. but there was now increased uptake in the right 9th and 10th ribs, and in the L5 and Sl vertebrae. Between June and December 1982, the pain was improved at all sites, but repeat x-rays showed marked deterioration of the osteolysis in all lower timb long bones, with a silent fracture of the right superior pubic ramus (Fig. 6). In June 1983, she developed a recurrence of severe pain in the left ankle

In summary, this 37.year-old woman had an unusual form of migratory osteolysis with successtve painful episodes involving numerous sites in the appendicular and axial skeleton, including the long bones, hands, feet, ribs. pelvis, and vertebrae, with several compression fractures. Recurrent episodes have occurred over a 5-year period and have tended to be followed by spontaneous improvement in symptoms, but there is little evidence of remineralization at involved sites

Discussion

Osteoporosis IS a usually generalized symmetrical disorder of bone. However, osteoporosis may be regional, that is, confined to a region or a segment of the body. Re- gional osteoporosis has been well reviewed by Resnick and Niwayama (1981), the major categories being immobilization or disuse, the reflex sympathetic dystrophy syndrome (including Sudeck’s atrophy and shoulderPhand syndrome), and transient regional osteoporosis. The pathogenesis of disuse osteoporosis is uncertain; the process may be somewhat reversible. Reflex sympathetic dystrophy may result from any neurally related visceral, musculoskeletal, neurological. or vascular condition. Its pathogenesis is also unclear, but It is presumed to be me- diated by efferent nerve impulses reflexly initrated within the spinal cord. Transient regional osteoporosis is characterized by rapidly developing osteoporosis affecting per-

V. Mavichak et al.: Migratory osteoporosis involving the vertebrae

Fig. 6. Case 3. a (left). Bone scan of both feet, March 1981, showing increased uptake in right ankle and in left foot. b (right). Bone scan of both feet, November 1981, showing improvement since March 1981, except for an increase in uptake in the right ankle.

iarticular bone, occurring in the absence of inciting events,

such as trauma or immobilization, and of a self-limited and reversible nature.

Two forms of transient regional osteoporosrs (which may be related) have been described: transient osteoporosis of the hip and regional migratory osteoporosis. Transient migratory osteoporosis of the hip was originally described in late pregnancy (Curtis and Kincaid, 1959) but can occur in other individuals, including males (Hunder and Kelly, 1968). Regional migratory osteoporosis most frequently afffects the knee, ankle, and foot and is most common In middle-aged males. It is characterized by local pain and swelling that develop rapidly, may last up to 9 months, and then decrease and disappear. Subsequent episodes involve the same or opposite extremity; several recurrences can occur within 2 years, or episodes may be separated by 2 or more years. Osteopenia becomes apparent within weeks or months of the clinical onset, pro- gresses rapidly and may subsequently diminish and occur at other sites. Bone scanning shows increased activity of involved areas. Usually, the joint nearest to the involved one is the next to be affected. In occasional patients only a single episode occurs in the hip (resulting in transient osteoporosis of the hip), knee (Corbett et al., 1977), or foot (Duncan et al., 1969). A variant of the syndrome, partial transient osteoporosis, involving only a portion of an articu-

lation, has been described by Lequesne et al. (1977). Ra- dial and zonal types have been delineated.

Vertebral osteoporosis occurring in association with regional migratory osteoporosis of lower extremities has not been previously reported, although the possibility was dis- cussed in a previous publication (Duncan et al., 1972). The presence of this association in our three patients sug- gests that regional migratory osteoporosis may not be confined to the appendicular skeleton. In Case 1 the clinical syndrome, with successive involvement of knee and foot in a 58-year-old man, was typical of regional migratory osteoporosis. Simultaneously, for the first time in his life, he had an episode of back pain, and x-rays showed vertebral compression fractures. Since he had not had previous x- rays, it is not certain whether the vertebral osteoporosis developed rapidly or had been present for some time. During his remaining 5 years of life the back pain com- pletely subsided. Further bone x-rays were not taken to show whether remineralization occurred in the involved areas; however, both the clinical syndrome and the abnor- malrties on bone scan resolved. Although impossible to prove, it seems likely that in this E&year-old man with typical regional migratory osteoporosis involving the legs, the simultaneous episode of vertebral fracturing may have re- sulted from involvement of the vertebrae by the same disease process.

348 V Mavtchak et al Migratory osteoporosis rnvolvlng the vertebrae

Fig. 7. Case 3 Lateral x-ray of dorsal spine, August 1981 showing compression fractures of T9 and T12 vertebrae

In Case 2, the assocration of osteoporosrs with pregnancy resembles in some respects other reported cases of acute osteoporosis in pregnancy (Gruber et al.. 1984). However, the diagnosis of migratory osteolysis is believed to be more appropriate In view of the clear migratory history and in view of the defrnite Improvement seen In the radiographs of her ankle.

Our Case 3 was unusual in that, unlike most reported cases of regional migratory osteoporosis. the patient’s skeletal lesions were not conftned to the lower limbs but involved arms, ribs, and pelvis as well as the spine. It IS possible that she actually suffered from a disorder distinct from Cases 1 and 2 and from other reported cases of ml- gratory regional osteoporosis These cases suggest that migratory regional osteoporosis may be responsible for some cases of apparently idiopathic spinal osteoporosis, with or without overt extravertebral involvement. In a recent prelrmrnary report, Dequeker et al. (1983) noted a high In- cidence of abnormalities In the appendicular skeleton in bone scans of patients with vertebral osteoporosis, an ob- servation that would also be consistent with this possibility Such involvement of the spine by transient migratory regional osteoporosis, with or without clinical evidence of In- volvement of the limbs, could be responsible for some cases of apparent idiopathic spinal osteoporosis in which the bone density is normal in the appendrcular skeleton (e.g. In the radius). This possibility would be suggested either by a history of typical episodes in the limbs in association with vertebral osteoporosis or by evidence on the bone scan of appendicular as well as axial involvement

It will be important to determine whether cases such as ours represent very rare examples of involvement of the spine by migratory regional osteoporosis or whether this IS a relatrvely frequent occurrence, since optrmal treatment of this disorder may well be different from that of typical se- nile or postmenopausal osteoporosis Finally, in common with other reports of migratory regional osteoporosis we have found no clues to the pathophysiology of this condr- tion In the three cases reported here and cannot therefore comment on appropriate treatment.

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Fig. 8. Case 3 Radiograph of pelvis, December 1982. showing fracture of right superior pubic ramus

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V. Mavichak et al : Migratory osteoporosis involving the vertebrae 349

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Recewed: August 30, 1985 Recewed: March 18, 1986

Accepted. April 7, 7986

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Regional migratory osteoporosis of the lower extremities with vertebral osteoporosis