JBJS | The Natural History of Osteonecrosis of the Femoral Head in Children and Adolescents Who Have Gaucher Disease*

The Journal of Bone & Joint Surgery, Volume 78, Issue 1

Articles | January 01, 1996

The Natural History of Osteonecrosis of the Femoral Head in Children and Adolescents Who Have Gaucher Disease*

KALMAN KATZ, M.D.†; GAD HOREV, M.D.†; MICHAEL GRUNEBAUM, M.D.†; ZVI YOSIPOVITCH, M.D.†, TEL AVIV, ISRAEL

*No benefits in any form have been received or will be received from a commercial party related directly or indirectly to the subject of this article. No funds were received in support of this study.

†Departments of Orthopedic Surgery (K. K. and Z. Y.) and Imaging (G. H. and M. G.), Schneider Children's Medical Center of Israel, Beilinson Medical Campus, Petah Tiqva 49202, Israel.

Investigation performed at the Departments of Orthopedic Surgery and Imaging, Schneider Children's Medical Center of Israel, Beilinson Medical Campus, Petah Tiqva, and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv

The Journal of Bone & Joint Surgery. 1996; 78:14-9

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Abstract

We reviewed the cases of eight patients (thirteen hips) with Gaucher disease who had had osteonecrosis of the femoral head and had been managed with bed rest and non-weight-bearing with crutches only in the symptomatic stage of the bone crisis. The mean age of the patients at the onset of the first crisis in each hip was ten years (range, six to fourteen years). The mean age at the most recent follow-up examination for the six living patients (ten hips) was twenty-three years (range, nineteen to thirty-three years). The Mose rating was good for one hip, fair for two, and poor for seven.Despite the over-all unfavorable radiographic ratings, the six patients were asymptomatic and did not need assistance with daily activities. There is no known treatment that effectively prevents the development of deformities of the femoral head. Thus, we recommend symptomatic management for osteonecrosis of the femoral head in Gaucher disease with bed rest and analgesics followed by non-weight-bearing on the involved limb, if it makes the patient more comfortable, during the symptomatic stage of bone crisis.

Figures in this Article

Introduction

Introduction | Materials and Methods | Results | Discussion | References

Gaucher disease is an autosomal recessive metabolic disorder characterized by abnormal accumulation of glucocerebroside in the reticuloendothelial cells due to a deficiency in glucosylceramide ß-glucosidase activity⁴.

There are three types of Gaucher disease. Type-I, non-neuronopathic, so-called adult Gaucher disease is the most common. The clinical manifestation of this type is largely splenomegaly associated with various degrees of pancytopenia. Infiltration of the bone marrow by Gaucher cells causes multiple skeletal manifestations. Bone pain is the most common, occurring in 35 to 83 per cent of patients who have type-I Gaucher disease^5,13. Various patterns of bone pain have been described, with non-specific dull pain of unknown origin that persists for one or two days being reported most often⁵. Severe pain may be due to a so-called bone crisis or may be associated with pathological fracture, osteomyelitis, or degenerative joint disease^8,16.

Type-II (acute neuronopathic) Gaucher disease appears in infancy and is associated with severe neurological abnormalities. The average duration of survival is nine months. Type-III (subacute neuronopathic) Gaucher disease is characterized by hepatosplenomegaly that appears in the first decade of life and neurological and skeletal manifestations that develop during childhood and adolescence. Most affected patients have convulsions⁴.

All of the patients in the present study had type-I Gaucher disease. A bone crisis of the femoral head, which radiographic and histological examination¹⁷ has suggested is usually the earliest clinical manifestation of osteonecrosis of the femoral head, is one of the most common skeletal manifestations of type-I Gaucher disease^1,2,8,16. The presenting symptoms of the crisis are the acute onset of severe pain that often cannot be relieved, even with the use of narcotics; local signs of redness, swelling, warmth, and tenderness around the involved bone; and often fever. The clinical signs last for a few days to several weeks. Non-specific laboratory findings during the crisis include an elevated erythrocyte sedimentation rate and polymorphonuclear leukocytosis. We believe that the severe pain at the onset of the crisis is caused by increased intraosseous pressure from edema and hemorrhage. Magnetic resonance images made at the time of the crisis show high-intensity intramedullary and subperiosteal signals, both in the T1 and T2-weighted sequences, suggesting hemorrhage⁶. The immediate relief of pain that has been noted after osseous decompression at the site of the crisis supports this theory¹⁷.

In one study, five of six patients who had osteonecrosis of the femoral head had bilateral involvement¹³. In most children and adolescents, the femoral head heals with marked deformity^2,14. Complete reconfiguration of the femoral head was observed at the ages of fourteen and fifteen years in two patients, reported on previously^3,7, who had been managed with bed rest and non-weight-bearing for three years. Poor results were noted in two children who had been managed with non-weight-bearing and an abduction splint¹⁴. To our knowledge, no data are available regarding operative treatment.

Owing to the generally poor prognosis of the osseous disease in affected children, symptomatic treatment consisting of non-weight-bearing with crutches has been recommended⁹. At our institution, all children and adolescents with Gaucher disease who had clinical manifestations of a bone crisis of the femoral head were managed with bed rest and analgesics for two to three weeks followed by non-weight-bearing (with the use of crutches) on the involved side for one to three weeks until the pain resolved. The long-term results are presented in this paper.

Materials and Methods

Introduction | Materials and Methods | Results | Discussion | References

Between 1960 and 1990, fifty-three patients of Ashkenazi Jewish origin who had type-I Gaucher disease were routinely followed according to the protocol of our institution and were seen when clinically indicated. The diagnosis of Gaucher disease was suspected because of splenomegaly and was confirmed in each patient by histopathological examination of biopsy specimens of marrow as well as appropriate enzyme studies. The patients were seen every six to twelve months, at which time the sizes of the spleen and liver were measured, the height and weight of the patient were recorded, and blood was drawn for a blood-cell count. The patients were also seen each time that they had pain, fever, or other symptoms. The patients were asked to report any bone pain and to come in for an examination at the onset of the pain. Twenty patients were seen at least once for bone pain. In all of them, radiographs of the involved bone showed some osseous changes, mainly expansion of the distal aspect of the femur, which had assumed an Erlenmeyer-flask appearance; increased radiolucency of bone; signs of osteonecrosis; and osseous fracture.

Eight patients (thirteen hips in four girls and four boys) were seen during the follow-up period with at least one episode of so-called bone crisis in one or both hips (Table I). When both hips were involved, the crises occurred on separate occasions. None of the children were managed with steroids before or after the onset of pain.

At presentation, all patients had clinical and radiographic examination of the involved site. Blood was drawn for routine studies and cultures. Follow-up radiographs of the hips were made at six weeks; three, six, and twelve months; and yearly thereafter until healing of the femoral head was noted. The criterion for healing was the appearance of an intact layer of subchondral bone. The age of the patient at the time of healing averaged thirteen years and ranged from nine to sixteen years.

Six patients were available for clinical and radiographic examination at the time of the latest follow-up. Two of the patients (three hips) died during the follow-up period, and their clinical findings are not included in this study. However, radiographs of the hips of these patients (Cases 3 and 5) were made twenty-eight, twenty-three, and twenty-four years after the onset of the symptoms in the hip, when the patients were thirty-six and thirty-four years old, and the findings on these radiographs are included in the Results section.

Pain in and function of the hip were assessed with the Iowa hip-rating system¹⁰. The maximum score for pain is 35 points, and the maximum score for function is also 35 points. Radiographs made during the active stage of the disease were examined for the extent of involvement of the femoral head and neck. The most recent follow-up radiographs were assessed with the Mose sphericity scale, which consists of a template of concentric circles outlined on a transparent material that is superimposed on anteroposterior and lateral radiographs. If the outline of the femoral head is a perfect circle on both radiographs, the hip is rated as good; if the deviation from the circle is two millimeters or less on both radiographs, the hip is rated as fair; and if the deviation is more than two millimeters on either the anteroposterior or the lateral radiograph, the hip is rated as poor^12,15.

Results

Introduction | Materials and Methods | Results | Discussion | References

The average age of the patients at the first so-called bone crisis in each hip was ten years (range, six to fourteen years) (Table I). Three patients (Cases 1, 3, and 4) had unilateral involvement, and five had bilateral involvement. When both hips were involved, the time between the onset of the crisis in one hip and the onset in the other hip ranged from one to three years. In two patients (Cases 7 and 8), recurrent crises followed by radiographic signs of osteonecrosis in both hips were noted during the follow-up period. The average duration of radiographic follow-up was fifteen years (range, five to twenty-eight years). The average duration of clinical follow-up was twelve years (range, five to twenty-four years). The average age at the most recent follow-up examination was twenty-three years (range, nineteen to thirty-three years) for the six patients (Cases 1, 2, 4, 6, 7, and 8) who were examined clinically.

At presentation, all of the patients had severe pain, swelling, and tenderness of the involved hip, with or without fever. The white blood-cell count ranged from 11,200 to 18,100 per cubic millimeter (11.2 to 18.1 x 10⁹ per liter), and the sedimentation rate ranged from fifty to ninety milliliters per hour. None of the hips were aspirated.

In six patients (eleven hips), periosteal elevation along the femoral neck six weeks after the onset of the crisis was the first radiographic manifestation (Figs. 1-A and 1-B). At the time of the most recent follow-up, the femoral neck was broad and short in all but one patient (Case 1), who had been seen because of a bone crisis at the age of six years. Six months after the onset of the crisis, a radiograph of the left femoral head showed a central area of resorption with good medial and lateral columns (Fig. 2-A). On the most recent follow-up radiographs, made when the patient was twenty-seven years old, the femoral head was spherical (Fig. 2-B). The patient was a medical registrar and had mild pain only after walking 1000 meters. The pain score was 30 points, and the function score was 35 points.

Anteroposterior radiographs of the other seven patients (Cases 2 through 8), made six to twelve months after the onset of the bone crisis, showed involvement of most or all of the femoral head. One of these patients (Case 2), who had a crisis in the right hip at the age of twelve years and in the left hip at the age of fourteen years, had fairly concentric femoral heads at the age of nineteen years. She served in the Israel Defense Force as a secretary and had pain only after walking 1000 meters or more. The pain score was 30 points and the function score was 32 points. The radiographs of the involved hips of the remaining six patients (Cases 3 through 8), who had an average age of twenty-seven years (range, nineteen to thirty-six years) at the time of the most recent follow-up, showed poor concentricity of the femoral heads. In four of the patients (Cases 3 through 6), the femoral head was ovoid (Figs. 3-A and 3-B). Two of these patients (Cases 4 and 6) were independent at the time of the most recent follow-up examination, worked full-time, and had pain only after walking approximately 500 to 1000 meters. The pain score for both was 30 points and the function scores were 35 and 32 points.

Three hips in two patients (Cases 7 and 8) had a flat, markedly deformed femoral head (Figs. 1-C and 1-D). Both patients had pain after walking approximately 500 to 1000 meters and a pain score of 30 points. One of the patients (Case 7), a religious scholar, had difficulty sitting and entering an automobile and a function score of 26 points. The other patient (Case 8), a community social worker, had a function score of 35 points.

Discussion

Introduction | Materials and Methods | Results | Discussion | References

Osteonecrosis of the femoral head is one of the most common skeletal manifestations of type-I Gaucher disease. Amstutz and Carey² reported that fifteen of twenty patients who had skeletal manifestations had osteonecrosis of the femoral head. Our findings that both hips are involved in most patients and that some patients have repeated events of osteonecrosis in the same hip support the observations of previous reports⁷.

The natural history and long-term follow-up of the osteonecrotic femoral head in children and adolescents who have Gaucher disease are rarely reported². The patients in the present study were managed with bed rest for two to three weeks and then with one to three weeks of non-weight-bearing on the involved limb, with the use of crutches. Patients were told to use the crutches without bearing weight as long as it was comfortable to do so and it helped to relieve the pain. In our opinion, short-term bed rest and the use of crutches did not alter the natural history of osteonecrosis of the femoral head in our patients. Even without treatment, a patient who has severe pain tends to stay in bed or to favor the affected limb. Thus, the reported findings are merely the outcome of the disease process.

We found that radiographic signs of involvement of the femoral neck may precede those of involvement of the femoral head by a few months. If a lesion is noted in the femoral neck on a radiograph made six weeks after the beginning of the crisis, involvement of the femoral head should also be suspected. In all but one hip, most or all of the femoral head showed signs of osteonecrosis during the active stage of the disease. The pathogenesis of the osseous changes along the femoral neck and head are not known.

The appropriate treatment during the active stage of osteonecrosis of the femoral head remains controversial. Good results were reported in two patients who were managed with non-weight-bearing for a few years^3,7. One of these patients was ten years old at the onset of the osteonecrosis and was followed until the age of fifteen years³. The other patient was six years old at the onset but did not have pain after that until the age of fourteen years, when a second crisis occurred in the same hip. Subsequently, despite long-term treatment with non-weight-bearing, the femoral head healed with deformities⁷. We believe, as do others¹¹, that the psychological problems and cost associated with long-term non-weight-bearing make it unacceptable. In previous reports, non-weight-bearing with use of crutches or an abduction brace resulted in irregular radiographic development of the femoral head in five of six hips in three children² and in two hips in two children¹⁴. These results are similar to the outcome of the disease process noted in our patients. Despite the poor radiographic appearance, all of our patients were asymptomatic and independent during daily activities. None had needed additional treatment, such as a total hip replacement, by the time of the most recent follow-up.

In conclusion, as no known treatment prevents the development of deformity of the femoral head, we recommend palliative treatment with bed rest and analgesics during the bone crisis, followed by non-weight-bearing on the affected limb with the use of crutches for as long as the patient finds this comfortable and helpful.

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TABLE I CLINICAL AND RADIOGRAPHIC FINDINGS FOR THE EIGHT PATIENTS (THIRTEEN HIPS)

*Only radiographic data are available for Cases 3 and 5, as they died before the most recent follow-up examination.†Maximum score, 35 points. NA = not available.

Case	Side	Age at First Crisis (Yrs.)	Age at Radiographic and Clinical Follow-up* (Yrs.)	Mose Rating	Iowa Hip Rating (Points)¹⁰
Pain†	Function†
1	L	6	27	Good	30	35
2	L	14	19	Fair	30	32
	R	12	19	Fair	30	32
3	L	8	36	Poor	NA	NA
4	L	9	33	Poor	30	35
5	L	11	34	Poor	NA	NA
	R	10	34	Poor	NA	NA
6	L	11	20	Poor	30	32
	R	12	20	Poor	30	32
7	L	13	19	Poor	30	26
	R	10	19	Poor	30	26
8	L	8	20	Poor	30	35
	R	6	20	Poor	30	35

TABLE I CLINICAL AND RADIOGRAPHIC FINDINGS FOR THE EIGHT PATIENTS (THIRTEEN HIPS)

*Only radiographic data are available for Cases 3 and 5, as they died before the most recent follow-up examination.†Maximum score, 35 points. NA = not available.

Case	Side	Age at First Crisis (Yrs.)	Age at Radiographic and Clinical Follow-up* (Yrs.)	Mose Rating	Iowa Hip Rating (Points)¹⁰
Pain†	Function†
1	L	6	27	Good	30	35
2	L	14	19	Fair	30	32
	R	12	19	Fair	30	32
3	L	8	36	Poor	NA	NA
4	L	9	33	Poor	30	35
5	L	11	34	Poor	NA	NA
	R	10	34	Poor	NA	NA
6	L	11	20	Poor	30	32
	R	12	20	Poor	30	32
7	L	13	19	Poor	30	26
	R	10	19	Poor	30	26
8	L	8	20	Poor	30	35
	R	6	20	Poor	30	35

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Figs. 1-A through 1-D: Case 8. Anteroposterior radiographs of the right hip. Fig. 1-A: In January 1978, six weeks after the onset of the bone crisis, at the age of six years, there was a thin line of periosteal elevation on the lateral side of the femoral neck (arrow).

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Fig. 1-B: In March 1978, there was periosteal elevation on both sides of the femoral neck.

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Fig. 1-C: In April 1979, there was fragmentation and loss of height of the femoral head, an irregular and wide growth plate, and a wide femoral neck.

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Fig. 1-D: In January 1992, there was flattening of the femoral head and the femoral neck was broad and short.

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Figs. 2-A and 2-B: Case 1. Anteroposterior radiographs of the left hip. Fig. 2-A: Six months after the onset of the bone crisis, when the patient was six years old, there was a central area of reabsorption of the femoral head with good medial and lateral columns.

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Fig. 2-B: Twenty-one years later, the femoral head was spherical.

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Figs. 3-A and 3-B: Case 4. Anteroposterior radiographs of the left hip. Fig. 3-A: One year after the onset of the bone crisis, when the patient was ten years old, there was fragmentation of the femoral head with a viable medial column and diffuse metaphyseal lesions.

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Fig. 3-B: Twenty-three years later, the femoral head was ovoid, with a short femoral neck.

References

Introduction | Materials and Methods | Results | Discussion | References

Amstutz, H. C.: The hip in Gaucher's disease. Clin. Orthop.,90: 83-89, 1973.9083 1973 [PubMed]

Amstutz, H. C., and |and |Carey, E. J.: Skeletal manifestations and treatment of Gaucher's disease. Review of twenty cases. J. Bone and Joint Surg.,48-A: 670-701, June 1966.48-A670 1966

Arkin, A. M., and |and |Schein, A. J.: Aseptic necrosis in Gaucher's disease. J. Bone and Joint Surg.,30-A: 631-641, July 1948.30-A631 1948

Brady, R. O., and Barranger, J. A.: Glucosylceramide lipidosis: Gaucher's disease. In The Metabolic Basis of Inherited Disease, edited by J. B. Stanbury, J. B. Wyngaarden, D. S. Fredrickson, J. L. Goldstein, and M. S. Brown. Ed. 5, pp. 842-856. New York, McGraw-Hill, 1983.

Goldblatt, J.; Sacks, S.; and |and |Beighton, P.: The orthopedic aspects of Gaucher disease. Clin. Orthop.,137: 208-214, 1978.137208 1978 [PubMed]

Horev, G.; Kornreich, L.; Hadar, H.; and |and |Katz, K.: Hemorrhage associated with "bone crisis" in Gaucher's disease identified by magnetic resonance imaging. Skel. Radiol.,20: 479-482, 1991.20479 1991

Katz, J. F.: Recurrent avascular necrosis of the proximal femoral epiphysis in the same hip in Gaucher's disease. Case report. J. Bone and Joint Surg.,49-A: 514-518, April 1967.49-A514 1967

Katz, K.; Mechlis-Frish, S.; Cohen, I. J.; Horev, G.; Zaizov, R.; and |and |Lubin, E.: Bone scan in the diagnosis of bone crisis in patients who have Gaucher disease. J. Bone and Joint Surg.,73-A: 513-517, April 1991.73-A513 1991

Lachiewicz, P. F.: Gaucher's disease. Orthop. Clin. North America,15: 765-774, 1984.15765 1984

Larson, C. B.: Rating scale for hip disabilities. Clin. Orthop.,31: 85-93, 1963.3185 1963 [PubMed]

Meehan, P. L.; Angel, D.; and |and |Nelson, J. M.: The Scottish Rite abduction orthosis for the treatment of Legg-Perthes disease. J. Bone and Joint Surg.,74-A: 2-12, Jan. 1992.74-A2 1992

Mose, K.: Methods of measuring in Legg-Calvé-Perthes disease with special regard to the prognosis. Clin. Orthop.,150: 103-109, 1980.150103 1980 [PubMed]

Silverstein, M. N., and |and |Kelly, P. J.: Osteoarticular manifestations of Gaucher's disease. Am. J. Med. Sci.,253: 569-577, 1967.253569 1967 [PubMed]

Todd, R. McL., and |and |Keidan, S. E.: Changes in the head of the femur in children suffering from Gaucher's disease. J. Bone and Joint Surg.,34-B(3): 447-453, 1952.34-B(3)447 1952 [CrossRef]

Weinstein, S. L.: Legg-Calvé-Perthes disease. In Lovell and Winter's Pediatric Orthopaedics, edited by R. T. Morrissy. Ed. 3, pp. 867-868. Philadelphia, J. B. Lippincott, 1990.

Yosipovitch, Z., and |and |Katz, K.: Bone crisis in Gaucher disease—an update. Israel J. Med. Sci.,26: 593-595, 1990.26593 1990 [PubMed]

Yosipovitch, Z. H.; Herman, G.; and |and |Makin, M.: Aseptic osteomyelitis in Gaucher's disease. Israel J. Med. Sci.,1: 531-536, 1965.1531 1965 [PubMed]

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Fig. 1-B: In March 1978, there was periosteal elevation on both sides of the femoral neck.

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Fig. 1-C: In April 1979, there was fragmentation and loss of height of the femoral head, an irregular and wide growth plate, and a wide femoral neck.

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Fig. 1-D: In January 1992, there was flattening of the femoral head and the femoral neck was broad and short.

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Fig. 2-B: Twenty-one years later, the femoral head was spherical.

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Fig. 3-B: Twenty-three years later, the femoral head was ovoid, with a short femoral neck.

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TABLE I CLINICAL AND RADIOGRAPHIC FINDINGS FOR THE EIGHT PATIENTS (THIRTEEN HIPS)

*Only radiographic data are available for Cases 3 and 5, as they died before the most recent follow-up examination.†Maximum score, 35 points. NA = not available.

Case	Side	Age at First Crisis (Yrs.)	Age at Radiographic and Clinical Follow-up* (Yrs.)	Mose Rating	Iowa Hip Rating (Points)¹⁰
Pain†	Function†
1	L	6	27	Good	30	35
2	L	14	19	Fair	30	32
	R	12	19	Fair	30	32
3	L	8	36	Poor	NA	NA
4	L	9	33	Poor	30	35
5	L	11	34	Poor	NA	NA
	R	10	34	Poor	NA	NA
6	L	11	20	Poor	30	32
	R	12	20	Poor	30	32
7	L	13	19	Poor	30	26
	R	10	19	Poor	30	26
8	L	8	20	Poor	30	35
	R	6	20	Poor	30	35

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TABLE I CLINICAL AND RADIOGRAPHIC FINDINGS FOR THE EIGHT PATIENTS (THIRTEEN HIPS)

*Only radiographic data are available for Cases 3 and 5, as they died before the most recent follow-up examination.†Maximum score, 35 points. NA = not available.

Case	Side	Age at First Crisis (Yrs.)	Age at Radiographic and Clinical Follow-up* (Yrs.)	Mose Rating	Iowa Hip Rating (Points)¹⁰
Pain†	Function†
1	L	6	27	Good	30	35
2	L	14	19	Fair	30	32
	R	12	19	Fair	30	32
3	L	8	36	Poor	NA	NA
4	L	9	33	Poor	30	35
5	L	11	34	Poor	NA	NA
	R	10	34	Poor	NA	NA
6	L	11	20	Poor	30	32
	R	12	20	Poor	30	32
7	L	13	19	Poor	30	26
	R	10	19	Poor	30	26
8	L	8	20	Poor	30	35
	R	6	20	Poor	30	35