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Electron microscopic changes in the osteoid of patients with fibrogenesis imperfecta ossium
146
Abstracts from the Bone and Tooth Society.
hormone; removal of mineral after incubation with bone cells removed the predisposition to osteoclastic resorption. These experiments indicate that one mechanism by which osteoblasts induce osteoclastic bone resorption may be through digestion of the unmineralized organic material present on all bone surfaces, to expose the underlying bone mineral to osteoclastic contact.
CHONDROCLASTS AND OSTEOCLASTS AT SUBCHONDRAL SITES OF CARTILAGE IN THE RHEUMATOID JOINT
EROSION
M. Bromley, J.M. Evanson, and D.E. Woolley Department of Medicine, Manchester, M20 8LR
University Hospital of South
Enzyme histochemical and ultrastructural studies have been performed on 21 specimens of cartilage-bone junction obtained from rheumatoid knee joints. Specimens were undecalcified and methacrylate embedded at 2°C to retain enzyme activity. Fifteen specimens showed multinucleated ceils identified as osteoclasts or chondroclasts. Chondroclasts are defined as multinucleate, acid phosphatase-positive cells with ruffled borders specifically associated with either mineralized or unmineralized cartilage, in contradistinction to osteoclasts which, although having similar morphologic and histochemical properties, are exclusively associated with mineralized bone. The extent of bone loss was variable, but where this had progressed to exposure of mineralized cartilage chondroclasts were consistently observed. Invasion of hyaline cartilage by bone-derived cells had occurred in 6 specimens, an observation invariably associated with the presence of chondroclasts. These cells were morphologically and histochemically similar to osteoclasts, demonstrating high acid phosphatase and ATPase staining. Acid phosphatase staining tended to be polarized toward the resorbing cartilage surface, and electron microscopy suggested active phagocytosis of collagen fibrils within a ruffled border. Our observations suggest that the multinucleate cells play a crucial role in subchondral destruction of mineralized bone and cartilage, indicating that articular cartilage of rheumatoid knee joints is vulnerable to bidirectional attack from synovial plannus and bone-derived cells. Work supported by the Arlhritis and Rheumatism Council.
FIBROGENESIS IMPERFECTA WITH MELPHALAN
OSSIUM REMITS
T.C.B. Stamp, P.D. Byers, S.Y. Ali, M.V. Jenkins, and J.M.T. Willoughby* The Metabolic Unit, lnsfitufe of Orthopaedics (University of London), Royal National Orthopaedic Hospital, Stanmore, Middlesex and lLister Hospital, Stevenage, Hertfordshire A patient with 6 years’ progressive bone pains and pathologic fractures showed hyperphosphatemia, bone radiographs with coarse or spotty trabeculae, bone history with excessive osteoid lacking birefringence and attenuated collagen fibrils-characteristics of fibrogenesis imperfecta ossium (FIO). Studies also revealed benign paraproteinemia.
A sequence of therapeutic experiments was undertaken. Calcitriol, with mineral supplementation, produced strongly positive calcium and phosphorus metabolic balances sustained in repeated studies over 16 months. Nevertheless he showed neither clinical, histologic, nor ultrastructural improvement. Hematology ultimately revealed myelomatosis and conventional melphalan therapy was added. Within 4 months he was almost painfree. Alkaline phosphatase flared, then normalized, and paraproteinemia disappeared. Further bone biopsy after 12 months showed normal osteoid volume, birefringence, and tetracycline uptake; fibrillar collagen was largely restored. Available reports of FIO now reveal coexistent paraproteinemia in 5 of 12 patients. Its present response to melphalan suggests that FIO may be caused by active product(s) or B-lymphocyte transformation that directly or indirectly disturb(s) collagen synthesis.
ELECTRON MICROSCOPIC CHANGES IN THE OSTEOID OF PATIENTS WITH FIBROGENESIS IMPERFECTA OSSIUM S.Y. Ali, J. Ralph% P. Dopping-Hepenstal, T.C.B. Stamp
and
Experimental Pathology Unit, lnsfitute of Orfhopaedics (University of London), Royal National Orthopaedic Hospital, Stanmore, Middlesex HA7 4LP Fibrogenesis imperfecta ossium (FIO) is a rare bone disease with a primary defect in the osteoid collagen. The wide, unmineralized osteoid in FIO is quite distinguishable from that in osteomalacia by its lack of normal lamellar pattern and birefringence in polarized light. The first iliac crest biopsy specimen from a 70-year-old male patient with clinical, radiologic, and histologic characteristics of FIO, showed a wide band of unmineralized osteoid with abnormal, random collagen fibrils, devoid of a lamellar pattern. Electron microscopy showed areas of thin, attenuated collagen fibrils, and others where collagen was either lacking or sparse, where an amorphous, presumably proteinaceous material was present. Scattered among the abnormal matrix were occasional microscopic foci of mineral, less than 0.5 pm in diameter. It appeared as if these mineral foci had gone past the initial crystal formation stage associated with matrix vesicles and had been halted in the second stage of crystal nodule formation before completing the third and final stage of bone mineral formation. The wide, disorganized osteoid in FIO was also associated with some cellular abnormalities which need further examination. A second biopsy taken a year after various therapeutic treatments showed no significant change. There was dramatic remission of the disease process following treatment with melphalan. Electron microscopy of the third biopsy showed that the osteoid had reverted to almost normal thickness, with birefringent, lamellar pattern and collagen fibrils. The abnormal proteinaceous deposits in the osteoid point to some inhibition of interference with mineral forination, and the coexistence of this with paraproteinemia in the patient may have some significance. Electron microscopy has proved a very useful tool in delineating this disease process both diagnostically, in showing the disorder in the osteoid, and in confirming the remission and return to normal bone formation.
Abstracts from the Bone and Tooth Society.
hormone; removal of mineral after incubation with bone cells removed the predisposition to osteoclastic resorption. These experiments indicate that one mechanism by which osteoblasts induce osteoclastic bone resorption may be through digestion of the unmineralized organic material present on all bone surfaces, to expose the underlying bone mineral to osteoclastic contact.
CHONDROCLASTS AND OSTEOCLASTS AT SUBCHONDRAL SITES OF CARTILAGE IN THE RHEUMATOID JOINT
EROSION
M. Bromley, J.M. Evanson, and D.E. Woolley Department of Medicine, Manchester, M20 8LR
University Hospital of South
Enzyme histochemical and ultrastructural studies have been performed on 21 specimens of cartilage-bone junction obtained from rheumatoid knee joints. Specimens were undecalcified and methacrylate embedded at 2°C to retain enzyme activity. Fifteen specimens showed multinucleated ceils identified as osteoclasts or chondroclasts. Chondroclasts are defined as multinucleate, acid phosphatase-positive cells with ruffled borders specifically associated with either mineralized or unmineralized cartilage, in contradistinction to osteoclasts which, although having similar morphologic and histochemical properties, are exclusively associated with mineralized bone. The extent of bone loss was variable, but where this had progressed to exposure of mineralized cartilage chondroclasts were consistently observed. Invasion of hyaline cartilage by bone-derived cells had occurred in 6 specimens, an observation invariably associated with the presence of chondroclasts. These cells were morphologically and histochemically similar to osteoclasts, demonstrating high acid phosphatase and ATPase staining. Acid phosphatase staining tended to be polarized toward the resorbing cartilage surface, and electron microscopy suggested active phagocytosis of collagen fibrils within a ruffled border. Our observations suggest that the multinucleate cells play a crucial role in subchondral destruction of mineralized bone and cartilage, indicating that articular cartilage of rheumatoid knee joints is vulnerable to bidirectional attack from synovial plannus and bone-derived cells. Work supported by the Arlhritis and Rheumatism Council.
FIBROGENESIS IMPERFECTA WITH MELPHALAN
OSSIUM REMITS
T.C.B. Stamp, P.D. Byers, S.Y. Ali, M.V. Jenkins, and J.M.T. Willoughby* The Metabolic Unit, lnsfitufe of Orthopaedics (University of London), Royal National Orthopaedic Hospital, Stanmore, Middlesex and lLister Hospital, Stevenage, Hertfordshire A patient with 6 years’ progressive bone pains and pathologic fractures showed hyperphosphatemia, bone radiographs with coarse or spotty trabeculae, bone history with excessive osteoid lacking birefringence and attenuated collagen fibrils-characteristics of fibrogenesis imperfecta ossium (FIO). Studies also revealed benign paraproteinemia.
A sequence of therapeutic experiments was undertaken. Calcitriol, with mineral supplementation, produced strongly positive calcium and phosphorus metabolic balances sustained in repeated studies over 16 months. Nevertheless he showed neither clinical, histologic, nor ultrastructural improvement. Hematology ultimately revealed myelomatosis and conventional melphalan therapy was added. Within 4 months he was almost painfree. Alkaline phosphatase flared, then normalized, and paraproteinemia disappeared. Further bone biopsy after 12 months showed normal osteoid volume, birefringence, and tetracycline uptake; fibrillar collagen was largely restored. Available reports of FIO now reveal coexistent paraproteinemia in 5 of 12 patients. Its present response to melphalan suggests that FIO may be caused by active product(s) or B-lymphocyte transformation that directly or indirectly disturb(s) collagen synthesis.
ELECTRON MICROSCOPIC CHANGES IN THE OSTEOID OF PATIENTS WITH FIBROGENESIS IMPERFECTA OSSIUM S.Y. Ali, J. Ralph% P. Dopping-Hepenstal, T.C.B. Stamp
and
Experimental Pathology Unit, lnsfitute of Orfhopaedics (University of London), Royal National Orthopaedic Hospital, Stanmore, Middlesex HA7 4LP Fibrogenesis imperfecta ossium (FIO) is a rare bone disease with a primary defect in the osteoid collagen. The wide, unmineralized osteoid in FIO is quite distinguishable from that in osteomalacia by its lack of normal lamellar pattern and birefringence in polarized light. The first iliac crest biopsy specimen from a 70-year-old male patient with clinical, radiologic, and histologic characteristics of FIO, showed a wide band of unmineralized osteoid with abnormal, random collagen fibrils, devoid of a lamellar pattern. Electron microscopy showed areas of thin, attenuated collagen fibrils, and others where collagen was either lacking or sparse, where an amorphous, presumably proteinaceous material was present. Scattered among the abnormal matrix were occasional microscopic foci of mineral, less than 0.5 pm in diameter. It appeared as if these mineral foci had gone past the initial crystal formation stage associated with matrix vesicles and had been halted in the second stage of crystal nodule formation before completing the third and final stage of bone mineral formation. The wide, disorganized osteoid in FIO was also associated with some cellular abnormalities which need further examination. A second biopsy taken a year after various therapeutic treatments showed no significant change. There was dramatic remission of the disease process following treatment with melphalan. Electron microscopy of the third biopsy showed that the osteoid had reverted to almost normal thickness, with birefringent, lamellar pattern and collagen fibrils. The abnormal proteinaceous deposits in the osteoid point to some inhibition of interference with mineral forination, and the coexistence of this with paraproteinemia in the patient may have some significance. Electron microscopy has proved a very useful tool in delineating this disease process both diagnostically, in showing the disorder in the osteoid, and in confirming the remission and return to normal bone formation.