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Active otosclerotic foci in the stapes. An electron microscopic study.

A total of 12 undecalcified and decalcified otosclerotic stapes containing active spongiotic lesions were examined using an electron microscope. Evidence of osteolytic osteolysis was seen in all specimens, but osteoclasts were observed in only four. The advancing front in the spongiotic lesion was 'moth-eaten' due to the demineralization of canaliculi and lacunae. The demineralizing process appeared to be initiated by degranulation of lysosomes by the degenerating osteocytes. As bone resorption continued, poorly mineralized new bone was laid down by osteoblasts which showed mitochondrial swelling. The possible implication of this mitochondrial swelling is discussed in relation to the pathology of the otosclerosis.

Ear Ossicles↗

A Japanese adult case of cystic fibrosis causing bone demineralization.

Cystic fibrosis is an inherited, multisystem disorder characterized by an abnormality in exocrine gland function. It leads to chronic pulmonary disease in most cases and pancreatic insufficiency in 85 percent of patients. Although this disease is not uncommon in Caucasians, it has been considered very rare among Japanese. The majority of patients are diagnosed in infancy or childhood. The patient in this case report was a 45-year-old Japanese man who had not been diagnosed as having cystic fibrosis. This patient had recurrent episodes of pulmonary infection that started in childhood, and plain films of the chest showed increased interstitial markings, hyperaeration, and bronchiectasis. CT of the upper abdomen showed a generally enlarged pancreas with complete fatty replacement. Serum and urine pancreatic enzyme levels were low, suggesting pancreatic insufficiency. Repeated sweat tests were positive. A roentgenologic skeletal survey showed general demineralization, which may be multifactorial. In this case, it was concluded that vitamin D deficiency caused by vitamin D malabsorption and/or insufficient sunlight exposure was mainly responsible for the demineralization and that chronic respiratory acidosis might also be partially responsible.

Bone and Bones↗

Relative accretion of 99mTc-polyphosphate by forming and resorbing bone systems in rats: its significance in the pathologic basis of bone scanning.

The relative roles of osteogenesis andd osteolysis in the production of positive radionuclide images of skeletal lesions were investigated. The uptake of 99mTc-polyphosphate (Tc-PP) by each process was measured in an animal model that permitted bone formation and resorption to be studied independently. Ten rats received intramuscular implants of bone-forming demineralized matrix (DM) and resorbing devitalized bone (DV). Radiographs and Tc-PP scintiscans were made each week thereafter. At 6-10 weeks, the implants and normal bone samples were removed, counted for 99mTc, and examined histologically. The uptake of Tc-PP BY DM implants was first detected on images made 3 weeks after implanatation, and by DV implants, 1-2 weeks later. Serial radiography showed progressive calcification of DM an resorption of DV implants. Microscopic examinations of undecalcified sections, stained with a modified Goldner preparation, revealed vital-bone formation in the DM implants and osteoclastic resorption in the DV. Activity counts per gram of DM and DV implants were, respectively, 200% and 90% that of normal bone. Since only the bone-forming system (DM) accumulated Tc-PP at greater than normal concentrations, this study indicates that positive bone images of osteolytic lesions solely reflect compensatory osteogenic responses.

Animals↗

Treatment of active unicameral bone cysts with percutaneous injection of demineralized bone matrix and autogenous bone marrow.

BACKGROUND: The treatment of unicameral bone cysts varies from open bone-grafting procedures to percutaneous injection of corticosteroids or bone marrow. The purpose of this study was to evaluate the feasibility and effectiveness of percutaneous injection of a mixture of demineralized bone matrix and autogenous bone marrow for the treatment of simple bone cysts. METHODS: Twenty-three patients with an active unicameral bone cyst were treated with trephination and injection of allogeneic demineralized bone matrix and autogenous bone marrow. The patients were followed for an average of fifty months (range, thirty to eighty-one months), at which time pain, function, and radiographic signs of resolution of the cyst were assessed. RESULTS: The average time until the patients had pain relief was five weeks, and the average time until the patients returned to full, unrestricted activities was six weeks. Bone-healing at the site of the injection was first seen radiographically at three to six months. No patient had a pathologic fracture during this early bone-healing stage. Cortical remodeling was seen radiographically by six to nine months, and after one year the response was usually complete, changing very little from then on. Five patients required a second injection because of recurrence of the cyst, and all five had a clinically and radiographically quiescent cyst after an average of thirty-six additional months of follow-up. Seven of the twenty-three patients had incomplete healing manifested by small, persistent radiolucent areas within the original cyst. None of these cysts increased in size or resulted in pain or fracture. CONCLUSIONS: Percutaneous injection of allogeneic demineralized bone matrix and autogenous bone marrow is an effective treatment for unicameral bone cysts.

Adolescent↗

Bone loss in spinal cord-injured patients: from physiopathology to therapy.

STUDY DESIGN: Review article on bone metabolism and therapeutic approach on bone loss in patients with spinal cord injury (SCI). OBJECTIVE: The first part aims to describe the process of bone demineralization and its effects on bone mass in patients with SCI. The second part describes and discusses the therapeutic approaches to limiting the alteration in bone metabolism related to neurological lesions. SETTING: Propara Rehabilitation Center, Montpellier, France. RESULTS: During the first 24 months postinjury, demineralization occurs exclusively in the sublesional areas and predominantly in weight-bearing skeletal sites such as the distal femur and proximal tibia, both of which are trabecular-rich sites. Reduced bone mass, in association with a modified bone matrix property and composition, is very likely at the origin of pathological fractures after minor trauma to which these patients are frequently exposed. Since these fractures may be asymptomatic yet may lead to complications, preventing and managing 'neurological osteoporosis' remains a considerable challenge. Two main approaches are considered: the first consists in applying a mechanical stimulus to the bone tissue by standing, orthotically aided walking or functional electrical stimulation (FES). The second uses medications, particularly antiresorptive drugs such as calcitonin or diphosphonates. CONCLUSION: To develop well-adapted treatments, a more precise understanding of bone loss etiology is needed. The current rehabilitation programs are based on the idea that the bone physiological changes observed in patients with SCI are due to immobility, but results indicate that alterations inherent to neurological damage may play an even greater role in inducing osteoporosis.

Bone Density↗

A randomized double blind placebo controlled trial of the effects on bone metabolism of the combination of nafarelin acetate and norethisterone.

OBJECTIVE: We observed the effects on bone metabolism of the addition of different doses of oral norethisterone during treatment with the GnRH agonist nafarelin (Synarel, Syntex). PATIENTS: Ninety-four women with a subjective complaint of heavy menstrual blood loss or objective evidence of endometriosis received intra-nasal nafarelin 400 micrograms daily for 6 months and also received, in a randomized, double blind manner, either 0.7 mg (n = 24), 1.4 mg (n = 23) or 2.45 mg (n = 23) of oral norethisterone or placebo (n = 24) daily. Follow-up was continued for a further 6 months after treatment. RESULTS: Thirty-one patients (33%) left the study prematurely and three patients were non-compliant with the study drug. By 6 months significant increases in urinary calcium/creatinine ratio were seen, compared to baseline, in the nafareline and placebo (P = 0.001, n = 14), 0.7 mg (P = 0.04, n = 13) and 1.4 mg norethisterone groups (P = 0.009, n = 17) but not in the nafarelin or 2.45 mg norethisterone groups (P = 0.72, n = 16). Densitometry of the spine, however, showed decreases at 6 months in all groups: 6.14% (P = 0.0004, n = 11), 5.46% n = 0.0006, n = 13), 3.93% (P = 0.008, n = 14) and 4.04% (P = 0.004, n = 16) for the groups receiving nafarelin and placebo, nafarelin and norethisterone 0.7, 1.4 and 2.45 mg respectively. Six months after stopping nafarelin, with or without norethisterone, bone mass was not different from baseline. CONCLUSION: The concomitant daily use of up to 2.45 mg of norethisterone does not eliminate the bone demineralization seen during GnRH agonist therapy with nafarelin in premenopausal women.

Administration, Oral↗

Otosclerotic stapes: morphological and microchemical correlates. An electron microscopic and x-ray analytical investigation.

A total of 32 otosclerotic stapes is thin-sectioned without decalcification and examined using transmission and scanning electron microscopes, with a nondispersive x-ray analyzer attached to the latter. These otosclerotic stapes are classified as spongiotic, sclerotic, or preotosclerotic, accoring to their pathologic characteristics and state of mineralization. Either diffuse or patchy demineralization in the ground substance appears to be the initial stage of otosclerosis, and this area coincides with preotosclerotic lesions (also known as blue mantle) in light microscopy. Therefore, it is interpreted that demineralization precedes the destruction of ground substance in the preotosclerotic lesion. Bone mineral deposits in new otosclerotic bone appear to be related to the collagen fibrils that are embedded in the ground substance. No mineral deposit could be seen without the ground substance deposition; therefore, it is suggested that this ground substance is the single most important factor in the poor mineralization of the otosclerosis. The sclerotic lesions are well mineralized and show a typical pattern of hydroxyapatite by x-ray diffraction study. We could not confirm the notion that the sclerotic lesion is hypermineralized as compared to the normal stapes. The spongiotic lesions are poorly mineralized, with low calcium salt. Using the Ca/P ratio and x-ray diffraction pattern as criteria, it was determined that spongiotic lesions belong to unstable, immature bone.

Bone Marrow↗

Bone matrix therapy for aneurysmal bone cysts.

Aneurysmal bone cysts are unique pathologic entities that cause pain and local osseous destruction. Many surgical treatment modalities have been described. This article reports on the case of a 16-year-old high school athlete with left heel pain due to an aneurysmal bone cyst in the calcaneus. Curettage of the bone cyst was performed, and the void was filled with a commercially available mixture of cancellous bone and demineralized bone matrix. Early return to athletic activity was achieved, with no recurrence noted at 3-year follow-up.

Adolescent↗

[Mineralization status in bones in patients with femoral neck fractures].

The authors present the results of the evaluation of the state of the art of mineralization of the bone in 56 patients over 45 years of age with the fracture of the femoral neck. The state of the art of mineralization was evaluated by means of bone indices. In each patient there were determined 6 values of bone indices and thus they got a more objective picture of the state of the art of bone tissue. They found out that most cases of fractures occurred on the osteporous skeleton. For pathological values corresponding to osteoporosis they considered such values when the bone index according to Barnet-Nordin was less than 45, Garn index less than 67, Singh index equal to the values I, II, III and Kocian index corresponded to normograms. Lower cortico-diaphyseal index on the side of the fracture in comparison with the contralateral side they explain by timely demineralization after the fracture during immobilization. Proceeding from the results achieved they emphasize the necessity of a timely prevention and treatment of osteoporosis.

Aged↗

Computed tomography of humans and bowed stringed instruments. Some interesting similarities.

We have used computed tomography to evaluate bowed stringed instruments and have noted interesting analogies with CT scans of humans. In humans, CT commonly detects a broad range of normal anatomic variations. Similarly, CT of violins and cellos demonstrates a wide range of normal structural variations. CT, often used to detect infections in humans, also detects defects from wood infestations. In humans, the unrelenting effect of gravity causes deformity of the demineralized spine. In old stringed instruments, plastic deformity of wood results from unrelenting string pressure. Trauma causes bone fractures in humans and wood fractures in bowed stringed instruments, and repairing fractures in both humans and stringed instruments requires various splitting devices. In summary, CT provides the physician and the luthier with a unique, noninvasive tool that can characterize the broad range of normal structures, pathological conditions, and repair.

Fractures, Bone↗

Periodontal & systemic bone changes in rats with experimental lathyrism.

BACKGROUND & OBJECTIVE: It is not clear how lathyrism affects the systemic bone metabolism. We therefore undertook a study to observe periodontal and systemic bone changes by performing radiological, metabolic, and bone densitometric evaluations in rats with experimental lathyrism. METHODS: A total of 30 rats were used. Experimental lathyrism was induced by once daily subcutaneous administration of beta-aminopropionitrile (beta-APN), at a dose of 5 mg beta-APN/0.4 ml per 100 g of body weight for 40 days. After 40 days, vertebral bone mineral density was analyzed by means of dual energy X-ray absorbtiometry in both groups. Blood was drawn by cardiac puncture and the animals were decapitated. Serum calcium levels were measured. Right mandibles were removed and radiographs were obtained. Alveolar bone level was determined in the radiographs. RESULTS: In all lathyritic rats, alveolar bone level was pathologically decreased with visible resorption. Vertebral bone mineral density values of lathyritic rats did not differ significantly from those of the control group. Compared to controls, there was a statistically significant decrease in serum calcium levels in the lathyritic group (P<0.001). INTERPRETATION & CONCLUSION: Significant alveolar bone resorption without alterations in vertebral bone mineral density indicated that lathyrogen administration for 40 days presumably has not caused systemic demineralization. This model could be used for studying the role of local and systemic agents on periodontal alveolar bone resorption.

Alveolar Process↗

[Focal demineralization of the cortical plate of the jaw and its experimental reversibility based on microphotometry data].

Focal demineralization of bone tissue with local dosed vacuum (exposure of up to 20 sec) and 2% lithium chloride electrophoresis (8 sessions daily, 10 min exposure) was tried in 40 white rats (21 reference ones and 19 experimental). The maximal reduction of mineral content was achieved on days 3-7 after the end of the course and made up 76.2 +/- 15.0% (p less than 0.01) and 80.6 +/- 12.5% (p less than 0.001), respectively, as against the reference animals. Mineral content at the site of demineralization gradually normalized by day 21. This transient reduction of mineral content of bone tissue may be used in orthodontic treatment of dentition abnormalities.

Alveolar Process↗

Chondrodysplasia punctata--rhizomelic form. Pathologic and radiologic studies of three infants.

Pathologic, ultrastructural and radiologic studies are described on 3 infants with the rhizomelic form of chondrodysplasia punctata. Radiologic criteria in the young infant include radiolucent coronal clefts dividing all or most of the thoracic and lumbar vertebral bodies, short humeri with flared metaphyses and punctate calcifications commonly present adjacent to the ossified ischial and pubic bones and less commonly in other locations. In late infancy and childhood the radiologic criteria include demineralization in all bones with slow maturation, flat vertebral bodies, short humeri and femora, metaphyseal flaring, especially in the distal humerus, proximal femur and proximal tibia, immature shape of pelvis, and disappearance of the punctate calcifications with advancing age. The histologic changes of the resting cartilage include areas of degenerating cartilage which had become partially calcified, cystic changes with severe disturbance of the maturation of the cartilage at the physial plate, and the formation of cancellous bone directly on resting cartilage. Ultrastructural changes are characterized by degeneration of chondrocytes, delicate collagenous fibrils without visible periodicity, and the presence of flocculent material within greatly distended endoplasmic reticulum.

Bone and Bones↗

[Physicochemical analysis of subcutaneous calcifications in a case of Thibierge-Weissenbach syndrome].

A physicochemical study of subcutaneous calcium deposits was performed in a patient with typical Thibierge-Weissenbach syndrome which had begun, ten years previously, with Raynaud's phenomenon and sclerodactylia. Calcium deposits had progressively developed, forming large plates on the arms, flanks and thighs. In the course of the disease they had become ulcerated, exuding a white, chalky material. X-ray films and xerograms demonstrated the extent of these deposits. The calcium-phosphorus balance was normal, and the other clinical and laboratory examinations were concordant with a diagnosis of Thibierge-Weissenbach syndrome (calcinosis). Only systemic corticosteroid therapy slowed down the pathological process; calcium chelating agents (diphosphonate) proved ineffective. The physicochemical study showed that the deposits consisted of carbonated apatite type B with the following formula: Ca8.0(PO4)4.1(CO3)1.2(HPO4)0.8 The mineral substance seemed to be less reactive and more stable than normal bone. This would account for the total lack of effectiveness of all treatments, notably calcium chelating agents, on the course of the deposits. Treatments usually produce bone demineralization before they influence the calcium deposits. This study provides much more detailed information than was hitherto available on calcium deposits and on carbonate ion contents in the apatite phase. The presence of carbonates increases the solubility and reactivity of calcium apatite.

Calcinosis↗

[The role of GnRH agonists in the endoscopic treatment of endometriosis and fibromyomas].

Uterine myomas and endometriosis are benign pathologies frequently encountered in women. Myomas are often associated with infertility and/or menorrhagia particularly if they are sub-mucosal. Endometriosis is diagnosed in more than 35% of infertile patients. These two common pathologies are oestrogen-dependent and the administration of a GnRH agonist has been proposed as a non-surgical approach to the treatment of myomas and endometriosis. GnRH agonists cannot, however, be considered as definitive medical therapy because most myomas and endometriotic cysts return to their initial size within 4 months following the cessation of treatment. Moreover, because of the menopausal-like state that they induce, GnRH agonists provoke bone demineralization and for this reason, their long-term use is not recommended. These agents should, therefore, be considered as an adjuvant preoperative therapy. The aim is, above all, to achieve a preoperative reduction of tumour size, thus facilitating the endoscopic surgery: either hysteroscopic resection in the case of sub-mucosal myomas, or vaporization of ovarian cysts in the case of cystic endometriotic lesions.

Adult↗

Pycnodysostosis: role and regulation of cathepsin K in osteoclast function and human disease.

Patients with pycnodysostosis, a rare skeletal dysplasia, present with bone abnormalities such as short stature, acroosteolysis of distal phalanges, and skull deformities. The disease is caused by a deficiency of the cysteine protease cathepsin K which is responsible for degradation of collagen type I and other bone proteins. Osteoclasts, bone cells of hematopoietic origin responsible for bone mineral as well as protein matrix degradation, are dysfunctional in patients with pycnodysostosis due to mutations in the cathepsin K gene. Cathepsin K deficient osteoclasts can demineralize bone but cannot degrade the protein matrix. Mutations in the cathepsin K gene disrupting wild type cathepsin K activity have been described in patients with pycnodysostosis. Animal models of cathepsin K deficiency have been created and provide a valuable tool to study osteoclast function and treatment for cathepsin K deficiency. Understanding the regulation and role of cathepsin K in osteoclast function is important for designing future therapies for pycnodysostosis. Cathepsin K inhibitors will be useful in pathological processes involving excess osteoclast activation and bone resorption such as osteoporosis, bone metastasis and multiple myeloma. This review will discuss the bone remodeling cycle, the human disease pycnodysostosis caused by cathepsin K deficiency and cathepsin K activity and regulation.

Bone and Bones↗

[Bone demineralization and elevation of serum osteocalcin concentrations in young children with hyperthyroidism].

Bone mineralization and serum osteocalcin level were evaluated in 15 children with Grave's disease. Two groups were constituted according to the presence (group I: n = 9) or absence (group II: n = 6) of a severe bone demineralization. A spontaneous fracture and a collapsed vertebra were found in one group I patient. Patients in group I were younger than in group II (8.3 +/- 4.9 vs 11.5 +/- 4.3 yrs). One patient in group II and six in group I were prepubertal with advanced bone age and increased growth velocity. Osteocalcin measurement (Oc) was performed in 10 patients (group I: n = 6; group II: n = 4) at the time of biological hyperthyroidism. The six patients with bone demineralization had elevated Oc levels. In group II, two patients had normal Oc levels and two had elevated Oc levels. In treated patients with good control of hyperthyroidism, all group II patients except one, had normal serum Oc levels and bone mineralization remain normal (n = 5) after 0.6 to 4.6 yrs of follow-up. In group I patients, although height velocity was normal, elevated (n = 4) or slightly elevated (n = 1) serum Oc levels and severe bone demineralization (n = 7 cases) persisted after 0.5 to 3 yrs of good control of the hyperthyroidism. Although the method used for measuring bone mineralization is potentially less precise than bone densitometry and not all the patients had serum osteocalcin measurements at the same time of the illness, our results emphasize that skeletal demineralization may be particularly marked in young children with Grave's disease and should be carefully evaluated.

Absorptiometry, Photon↗