Scand I Haematol(l979) 22, 339-342
CASE REPORT
Osteogenesis Irnperfecta Associated with Multiple Myeloma M. KUTNOWSKI, B. FUTERAL, M. VERBANCK, J. P. NAETS& J. P. MULLIER Department of Medical Hospitalization and Department of Haematology, Brugmann Hospital, Free University of Brussels, Belgium
In a case of osteogenesis imperfecta with multiple fractures already from childhood, myelomatosis was diagnosed at the age of 52 years because of a serum M-component (IgG, lambda), Bence Jones proteinuria, myeloma cells in the bone marrow, and osteolytic skeletal lesions. She died 10 months later. A partial postmortem examination of a larger bone lesion confirmed the diagnosis.
Key words: multiple myeloma - osteogenesis imperfecta Accepted for publication February 26, 1979 Correspondence to: Dr. M. Kutnowski, Department of Medical Hospitalization, Brugmann Hospital, 4, Square Van Gehuchten, B-1020 Brussels, Belgium
Osteogenesis imperfecta (01) is a hereditary unusual disease of the connective tissue and with the clinical features multiple bone fractures, blue sclerae, progressive deafness, hyperlaxity of ligaments, dental troubles and thin skin. In 01 congenita (Vrolik’s type), symptoms are already present at birth; in 01 tarda (Lobstein’s type) the clinical signs may be mild or severe and the diagnosis is usually made during adolescence or later in life. The primary defect in 01 lies in an abnormality of the collagen fibers. Argyrophilic and PAS-positive fibers, corresponding to small collagen fibers, take their place (Bondy & Rosenberg 1974). Scanning electron microscopy studies show bone collagen aggregation abnormalities: the bonds be-
tween the fibrils are scarce and the interfibrillary spaces are too wide, as stated by Teitelbaum et a1 (1974). The proline incorporation rate in collagen seems to be abnormally low (Jaffe 1972). Francis et a1 (1975) suggested that the clinical differences between patients with 01 may be attributed to various disturbances in the aminoacid sequence. Stimulation of the oxydative metabolism noted by Cropp (1973) seems to be related to high T3 and T4 values. The plasma and the urinary hydroxyproline excretion is usually slightly increased (Bondy & Rosenberg 1974, Dulce 1975). The same trend may be seen for alkaline (Dulce 1975) and acid phosphatases (Gebala 1956), a controversial issue for Ginsberg (1962).
0036-553W79/040339-04 $02.50/0 @ 1979 Munksgaard, Copenhagen
OSTEOGENESIS IMPERFECTA AND MYELOMA
Figure 2. Blue sclerae of the patient.
341
morphological characteristics of young plasma cells were seen in the medulla. Bone scan. A pyrophosphate bone scan dernonstrated multiple pathological foci (right shoulder, ribs, dorsal and lumbar column, right hip, and left ankle). The diagnosis of IgG myeloma was obvious. Chemotherapy with melphalan (10 mg/d) and prednisolone (100 mg/d) in an intermittent schedule was started. This treatment was associated with N a F (50 mg/d) and vitamin C (1.5 g/d). A regular follow up was carried out. The treatment brought about a certain degree of alleviation of the back pain. 9 months after the first admission the pa-
Figure 3. X-ray picture of pelvic bones showing the osteolytic lesion of the. left ileum. tient was readmitted in a state of respiratory ESR (Westergren 1 h) = 128 mrn, prothrombin distress due to a post-influenza broncho- time 42 %, acid phosphatase 1.28 Sigma Units pneumonia. Besides clinical evidence of lower (normal range 0.13-0.63). The X-rays film showed bilateral pulmonary consolidation, there was multiple rib fractures. The clinical situation soreness on percussion of the ribs. Abdominal gradually deteriorated. 5 d after admission, a examination revealed a painful mass in the left spontaneous fracture occurred at the proximal lower quadrant. metaphysis of the left femur, complicated by a Biochemical findings. Blood urea 64 mg/dl, voluminous haematoma. creatinine 3 mg/dl, RBC 3900000/ml, Hb 98 gA, The patient died in a state of marasmus 3 PCV 30 %, WBC 4.7 x lo9/], platelets 134 x lo9/& weeks after hospitalization. Only a partial post-
342
KUTNOWSKI, FUTERAL, VERBANCK, NAETS & MULLIER
mortem examination was performed. Microscopic examination of the iliac mass confirmed the diagnosis of a plasmatocytoma. COMMENTS
Association of 01 with another disease is rarely seen; nevertheless, it has been described with mitral regurgitation (Heckman & Steinberger 1968) and hyperparathyroidism (Salti et a1 1973, Woolfson et a1 1975). The association of osteogenesis imperfecta and multiple myeloma has obviously not been described before. REFERENCES Bondy P K & Rosenberg L E (1974) Duncan’s diseases of metabolism, Vol 1,931-33. Saunders, Philadelphia / London / Toronto. Cropp G J A (1973) Hypermetabolism in osteogenesis imperfecta. In B Frame, A M Parfitt & H Duncan (eds) Clinical aspects of metabolic bone disease, pp 308-13. Excerpta Medica, Amsterdam. Dulce H J (1975) Biochemistry of bone diseases. In F Kuhlencordt & H P Kruse (eds) Calcium metabolism, bone and metabolic bone diseases, pp 197-207. Springer Verlag, Berlin / Heidelberg / New York. Francis M G 0, Smith R & Bauze R G (1975) A clinical and biochemical survey of osteogenesis imperfecta with evidence for a generalized collagen defect. In F Kuhlencordt & H P
Kruse (eds) Calcium metabolism, bone and metabolic bone diseases, pp 221-25. Springer Verlag, Berlin / Heidelberg / New York. Gebala A (1956) Acid hyperphosphatasia in three families with osteogenesis imperfecta. Lancet 2, 1084. Ginsberg D M (1962) Normal serum acid phosphatase levels in osteogenesis imperfecta. Ann Intern Med 56, 14143. Heckman B A & Steinberg I (1968) Congenital heart disease (mitral regurgitation) in osteogenesis imperfecta. Am J Roentgen01 103, 60160. Jaffe H L (1972) Metabolic, degenerative and inflammatory diseases of bones and joints, p 162. Urban and Schwarzenberg, Munich / Berlin / Vienna. Salti I S, Nassar V H & Bulos S (1973) The coexistence of primary hyperparathyroidism and osteogenesis imperfecta. Can Med Assoc J 108, 883. Stanbury J B, Wyngaarden J B & Frederickson D S (1972) The metabolic basis of inherited disease, p 1696. McGraw-Hill, New York / Toronto / Sydney / London. Teitelbaum S L, Kraft W J, Lang R & Avidi L V (1974) Bone collagen aggregation abnormalities in osteogenesis imperfecta. Calcif Tissue Res 17, 75-79. Woolfson AM, Fleming J A & Steward J S (1975) A palpable parathyroid tumor in a patient with osteogenesis imperfecta. Proc R Soc Med 65, 61-62. Worth Estes J (1968) Platelets size and function in the heritable disorders of connective tissue. Ann Intern Med 68, 1237-49.
CASE REPORT
Osteogenesis Irnperfecta Associated with Multiple Myeloma M. KUTNOWSKI, B. FUTERAL, M. VERBANCK, J. P. NAETS& J. P. MULLIER Department of Medical Hospitalization and Department of Haematology, Brugmann Hospital, Free University of Brussels, Belgium
In a case of osteogenesis imperfecta with multiple fractures already from childhood, myelomatosis was diagnosed at the age of 52 years because of a serum M-component (IgG, lambda), Bence Jones proteinuria, myeloma cells in the bone marrow, and osteolytic skeletal lesions. She died 10 months later. A partial postmortem examination of a larger bone lesion confirmed the diagnosis.
Key words: multiple myeloma - osteogenesis imperfecta Accepted for publication February 26, 1979 Correspondence to: Dr. M. Kutnowski, Department of Medical Hospitalization, Brugmann Hospital, 4, Square Van Gehuchten, B-1020 Brussels, Belgium
Osteogenesis imperfecta (01) is a hereditary unusual disease of the connective tissue and with the clinical features multiple bone fractures, blue sclerae, progressive deafness, hyperlaxity of ligaments, dental troubles and thin skin. In 01 congenita (Vrolik’s type), symptoms are already present at birth; in 01 tarda (Lobstein’s type) the clinical signs may be mild or severe and the diagnosis is usually made during adolescence or later in life. The primary defect in 01 lies in an abnormality of the collagen fibers. Argyrophilic and PAS-positive fibers, corresponding to small collagen fibers, take their place (Bondy & Rosenberg 1974). Scanning electron microscopy studies show bone collagen aggregation abnormalities: the bonds be-
tween the fibrils are scarce and the interfibrillary spaces are too wide, as stated by Teitelbaum et a1 (1974). The proline incorporation rate in collagen seems to be abnormally low (Jaffe 1972). Francis et a1 (1975) suggested that the clinical differences between patients with 01 may be attributed to various disturbances in the aminoacid sequence. Stimulation of the oxydative metabolism noted by Cropp (1973) seems to be related to high T3 and T4 values. The plasma and the urinary hydroxyproline excretion is usually slightly increased (Bondy & Rosenberg 1974, Dulce 1975). The same trend may be seen for alkaline (Dulce 1975) and acid phosphatases (Gebala 1956), a controversial issue for Ginsberg (1962).
0036-553W79/040339-04 $02.50/0 @ 1979 Munksgaard, Copenhagen
OSTEOGENESIS IMPERFECTA AND MYELOMA
Figure 2. Blue sclerae of the patient.
341
morphological characteristics of young plasma cells were seen in the medulla. Bone scan. A pyrophosphate bone scan dernonstrated multiple pathological foci (right shoulder, ribs, dorsal and lumbar column, right hip, and left ankle). The diagnosis of IgG myeloma was obvious. Chemotherapy with melphalan (10 mg/d) and prednisolone (100 mg/d) in an intermittent schedule was started. This treatment was associated with N a F (50 mg/d) and vitamin C (1.5 g/d). A regular follow up was carried out. The treatment brought about a certain degree of alleviation of the back pain. 9 months after the first admission the pa-
Figure 3. X-ray picture of pelvic bones showing the osteolytic lesion of the. left ileum. tient was readmitted in a state of respiratory ESR (Westergren 1 h) = 128 mrn, prothrombin distress due to a post-influenza broncho- time 42 %, acid phosphatase 1.28 Sigma Units pneumonia. Besides clinical evidence of lower (normal range 0.13-0.63). The X-rays film showed bilateral pulmonary consolidation, there was multiple rib fractures. The clinical situation soreness on percussion of the ribs. Abdominal gradually deteriorated. 5 d after admission, a examination revealed a painful mass in the left spontaneous fracture occurred at the proximal lower quadrant. metaphysis of the left femur, complicated by a Biochemical findings. Blood urea 64 mg/dl, voluminous haematoma. creatinine 3 mg/dl, RBC 3900000/ml, Hb 98 gA, The patient died in a state of marasmus 3 PCV 30 %, WBC 4.7 x lo9/], platelets 134 x lo9/& weeks after hospitalization. Only a partial post-
342
KUTNOWSKI, FUTERAL, VERBANCK, NAETS & MULLIER
mortem examination was performed. Microscopic examination of the iliac mass confirmed the diagnosis of a plasmatocytoma. COMMENTS
Association of 01 with another disease is rarely seen; nevertheless, it has been described with mitral regurgitation (Heckman & Steinberger 1968) and hyperparathyroidism (Salti et a1 1973, Woolfson et a1 1975). The association of osteogenesis imperfecta and multiple myeloma has obviously not been described before. REFERENCES Bondy P K & Rosenberg L E (1974) Duncan’s diseases of metabolism, Vol 1,931-33. Saunders, Philadelphia / London / Toronto. Cropp G J A (1973) Hypermetabolism in osteogenesis imperfecta. In B Frame, A M Parfitt & H Duncan (eds) Clinical aspects of metabolic bone disease, pp 308-13. Excerpta Medica, Amsterdam. Dulce H J (1975) Biochemistry of bone diseases. In F Kuhlencordt & H P Kruse (eds) Calcium metabolism, bone and metabolic bone diseases, pp 197-207. Springer Verlag, Berlin / Heidelberg / New York. Francis M G 0, Smith R & Bauze R G (1975) A clinical and biochemical survey of osteogenesis imperfecta with evidence for a generalized collagen defect. In F Kuhlencordt & H P
Kruse (eds) Calcium metabolism, bone and metabolic bone diseases, pp 221-25. Springer Verlag, Berlin / Heidelberg / New York. Gebala A (1956) Acid hyperphosphatasia in three families with osteogenesis imperfecta. Lancet 2, 1084. Ginsberg D M (1962) Normal serum acid phosphatase levels in osteogenesis imperfecta. Ann Intern Med 56, 14143. Heckman B A & Steinberg I (1968) Congenital heart disease (mitral regurgitation) in osteogenesis imperfecta. Am J Roentgen01 103, 60160. Jaffe H L (1972) Metabolic, degenerative and inflammatory diseases of bones and joints, p 162. Urban and Schwarzenberg, Munich / Berlin / Vienna. Salti I S, Nassar V H & Bulos S (1973) The coexistence of primary hyperparathyroidism and osteogenesis imperfecta. Can Med Assoc J 108, 883. Stanbury J B, Wyngaarden J B & Frederickson D S (1972) The metabolic basis of inherited disease, p 1696. McGraw-Hill, New York / Toronto / Sydney / London. Teitelbaum S L, Kraft W J, Lang R & Avidi L V (1974) Bone collagen aggregation abnormalities in osteogenesis imperfecta. Calcif Tissue Res 17, 75-79. Woolfson AM, Fleming J A & Steward J S (1975) A palpable parathyroid tumor in a patient with osteogenesis imperfecta. Proc R Soc Med 65, 61-62. Worth Estes J (1968) Platelets size and function in the heritable disorders of connective tissue. Ann Intern Med 68, 1237-49.
