Magnesium whitlockite, a calcium phosphate crystal of special interest in pathology.

Whitlockite (in fact magnesium whitlockite) is a calcium orthophosphate crystal in which, in biological conditions, magnesium is partly substituted for calcium. Identified in X-ray or electron diffraction patterns, it occurs in physiological or pathological conditions at extra or intratissular sites, mainly in tissues of non-epithelial origin. In a range of pathological calcifications investigated by X-ray diffraction, we noted that whitlockite appeared to be frequently associated with apatite, particularly in "dystrophic calcifications" of tuberculous origin. These personal observations could be correlated with documented data in oral pathology (dental calculus, salivary stones, and dental caries). Whitlockite deposits have also been reported in non-infectious conditions, such as in aortic media, cartilage, and bone tissue. Whereas the formation of both apatite and magnesium whitlockite appears to be caused by the binding of their constituting ions with proteolipids, magnesium inhibits apatite originating from amorphous calcium phosphate to the benefit of whitlockite formation. Possibly, the development of magnesium whitlockite may provide an interesting marker for magnesium metabolism. Further studies linking histology to crystallography might relate the crystal to issues, such as tuberculous calcifications or diseases of bone tissue, and might be useful for potential diagnostic orientation.

Metastatic carcinoma of presumed prostatic origin in cremated bones from the first century A.D.

A cremated pelvis dating from the first century A.D. showed evidence of osteosclerotic metastasis, presumably secondary to prostate carcinoma. The case demonstrates the importance of microradiography in palaeopathology as well as some of the structural changes seen in cremated bone.

[Heterogeneity of involutional osteoporosis]. / L'hétérogénéité des ostéoporoses d'involution.

Bone tissue mineral content (BTMC) was measured on transiliac bone biopsies by a combined microradiographic-microdensitometric technique. The samples originated from 69 osteoporotic postmenopausal women aged 42-86 (mean age 63 years). The diagnosis of osteoporosis was based upon a previous in-hospital screening. Results demonstrated a clear heterogeneity of BTMC values in osteoporotic women as compared with an age-related decrease in 31 age- and sex-matched controls. No correlation with clinical parameters could be found: Therapeutic issues raised by this study are discussed.

Structural changes of the periosteocytic area in Vipera aspis (L.) (Ophidia, Viperidae) bone tissue in various physiological conditions.

Microradiographs of ribs and vertebrae of the snake Vipera aspis, over an annual cycle, show a significant enlargement of the osteocytic lacunae in the winter months and, for the breeding females, during the period of embryo development. This enlargement is due to resorption of bone substance (periosteocytic osteolysis). The objection that such morphological findings could as well be explained by the formation of new, larger osteocytes derived from recent osteoblasts does not apply to the present animal model. No internal bone remodelling occurs during the annual seasonal cycle and therefore no new osteoblasts would have differentiated to osteocytes in the interior of the bone. In the vertebrae, an additional process is indicated as an area of decreased mineral density, termed demineralization halo, around the periosteocytic lacunae. An electron microscopy study suggests that this process of demineralization is not the first stage of periosteocytic resorption, but an additional process of demineralization. Thus, both osteolysis and demineralization halos in the perilacunar osteocytic region of the bone tissue represent reversible biological processes mediated by the osteocytes.

Rheumatic diseases in Neolithic and Medieval populations of western Switzerland.

An investigation of three groups from ancient populations (Neolithic, Early Middle Ages, Middle Ages) was performed on 273 adult skeletons. Despite unequal preservation of the remains, a study of a series of large joints and spinal segments permitted some conclusions: rheumatoid arthritis, ankylosing spondylitis, and osteoarthrosis of large joints (hip, knee, shoulder) were not found. The main findings were: osteoarthrosis in spinal zygapophyseal joints (particularly at cervical level); intervertebral osteochondrosis (particularly at the cervical and lumbar levels); Schmorl's nodes (particularly at the thoracic and lumbar levels); enthesopathic osteophytes (particularly in the spine, iliac crest, patella, and calcaneus). Such deformities seemed more frequent in the Middle Ages than in the Neolithic period.

A biophysical study of posttraumatic ectopic ossification. A case report.

Sites of ectopic ossification (EO) due to sports injury in a long-distance runner were biopsied and analyzed. The mineral content was compared to that of normal adult bone and to paraosteoarthropathy (POA) using biophysical methods. The degree of mineralization of bone tissue (DMBT) was employed as an evaluation of maturity of calcified tissue. Fluoride and carbonate content were determined. The crystal lattice dimensions expressed by the a and c parameters, crystal size, and/or lattice perfection were obtained with x-ray diffraction. All values were near those found in nonpathologic, newly deposited human compact bone. DMBT, crystal size, and/or lattice perfection were near those observed in a 24- to 30-month-old POA. The data suggest that posttraumatic EO represents otherwise normal young bone.

A historic skeleton with osteomyelosclerosis.

A case of osteomyelosclerosis (ie, an advanced stage of the myeloproliferative disorder named myelofibrosis) was reported in an adult male skeleton dating from the 17th or 18th century. The diagnosis was founded on the presence of a newly formed microspongiosa and a thickening of the preexisting trabeculae. A subperiosteal thickening of the cortical bone was also noted.

Skeletal fluorosis: histomorphometric findings.

Histomorphometric analysis of undecalcified sections was performed in transiliac biopsy cores taken from 29 patients (16 men, 13 women, aged 51 +/- 17 years) suffering from skeletal fluorosis due to chronic exposure to fluoride. The origin of the exposure, known in 20 patients, was either by water (endemic or sporadic), or industrial, or in a few cases iatrogenic. Measured on calcified bone using a specific ion electrode, bone fluoride content was significantly high in each specimen (mean +/- SD: 0.79 +/- 0.36% of bone ash) as compared to control values (less than 0.10%). The radiologically evident osteosclerosis observed in each patient was confirmed by the significant increase of cancellous bone volume (40.1 +/- 11.2 vs. 19.0 +/- 2.8% in controls, p less than 0.0001). There were significant increases in cortical width (1292 +/- 395 vs. 934 +/- 173 microns, p less than 0.0001) and porosity (14.4 +/- 6.4 vs. 6.5 +/- 1.7%, p less than 0.002), but without reduction of cortical bone mass. Osteoid parameters were significantly increased in fluorotic patients. The increase in cancellous osteoid perimeter was almost threefold greater than that noted in cancellous eroded perimeter. The fluorotic group had a greater number of osteoblasts than controls, with a very high proportion of flat osteoblasts. In 15 patients doubly labeled with tetracycline, the mineral apposition rate was significantly decreased, while mineralization lag time significantly increased. Bone formation rate and adjusted apposition rate were significantly decreased in skeletal fluorosis. Cancellous wall width was normal in fluorosis but the formation period and active formation period were significantly increased.(ABSTRACT TRUNCATED AT 250 WORDS)

Topographical distribution of fluoride in iliac bone of a fluoride-treated osteoporotic patient.

The electron microprobe was used to display the topographical distribution pattern of fluoride (F) at the microscopical level in the iliac bone of an osteoporotic patient treated with fluoride. Composite x-ray image of F K alpha emission revealed a high concentration of fluoride in the periosteal and endosteal bone layers, in the cancellous bone, and in certain osteons, which corresponded to the bone formed during the period of fluoride treatment. Fluoride was also concentrated around the Haversian canals in the vicinity of the capillary blood vessels by a diffusion process. Morphometric analysis showed that more cancellous bone than cortical bone is formed.

Multiple bone islands in a skeleton dating from the Neolithic period.

Multiple bone islands were observed in a skeleton dating from the Neolithic period (two in a femoral head, two in the lower epiphysis of a femur, one in a humeral head). Macroscopic and radiographical examination was complemented by microradiography in the femoral head.

Osteoarthrosis and apatite synovitis. Pathological study of a metacarpophalangeal joint.

A case of metacarpophalangeal osteoarthrosis associated with synovial apatite deposits is reported. The size of the crystals indicates that they have been thickened by a recrystallization process; the latter could have been provoked by Ca and Po4 ions released by dissolution of some apatite crystals brought by calcified debris of bone or cartilage coming from the abraded osteoarthrotic surfaces. The role of such thickened crystals in synovial inflammation is discussed as well as their possible diagnostic value in determining origin and pathogenesis of a given synovial apatite deposit.

Skeletal fluorosis: histomorphometric analysis of bone changes and bone fluoride content in 29 patients.

Bone fluoride content (BFC) was measured and histomorphometric analysis of undecalcified sections was performed in transiliac biopsy cores from 29 patients (16 men, 13 women, aged 51 +/- 17 years) suffering from skeletal fluorosis due to chronic exposure to fluoride. The origin of the exposure, known in 20 patients, was either hydric (endemic or sporadic) or industrial, or in a few cases iatrogenic. Measured on calcined bone using a specific ion electrode, BFC was significantly high in each specimen (mean +/- SD; 0.79 +/- 0.36% on bone ash). The radiologically evident osteosclerosis observed in each patient was confirmed by a significant increase in cancellous bone volume (40.1 +/- 11.2% vs. 19.0 +/- 2.8% in controls, p less than 0.0001). There were significant increases in cortical width (1292 +/- 395 mcm vs. 934 +/- 173 mcm, p less than 0.0001) and porosity (14.4 +/- 6.4% vs. 6.5 +/- 1.7%, p less than 0.002), but without reduction of cortical bone mass. Cancellous osteoid volume and perimeter, as well as width of osteoid seams, were significantly increased in fluorotic patients. The increase in cancellous osteoid perimeter was almost three-fold greater than that noted in cancellous eroded perimeter. In 15 patients doubly labeled with tetracycline, the mineral apposition rate was significantly decreased, mineralization lag time was significantly increased. The fluorotic group had a greater number of osteoblasts than controls with a very high proportion of flat osteoblasts. The ultrastructural characteristics reflecting the activity of the bone cells were clearly visible on electron microscopy. Bone formation rate and adjusted apposition rate were significantly decreased in skeletal fluorosis. On stained sections and microradiographs, bone tissue showed typical modifications for skeletal fluorosis (linear formation defects, mottled bone). The volume of cancellous interstitial mineralization defects and the proportion of mottled periosteocytic lacunae were markedly increased in skeletal fluorosis. These two parameters were significantly correlated together but neither of these was significantly correlated with BFC. Renal function did not significantly influence the changes in BFC and histomorphometry of fluorotic patients. Skeletal fluorosis is thus characterized by an unbalanced coupling in favor of bone formation, and a great number of osteoblasts with a high proportion of flat osteoblasts.(ABSTRACT TRUNCATED AT 400 WORDS)

Fluoride content in human iliac bone: results in controls, patients with fluorosis, and osteoporotic patients treated with fluoride.

The major part of fluoride ingested is fixed on calcified tissues, mainly in bone tissue, and then is progressively but slowly recycled during bone remodeling. Thus, the measurement of bone fluoride content allows the determination of the extent of bone fluoride retention, and this parameter constitutes a useful complement to bone histology for the diagnosis of skeletal fluorosis and could also be used for the management of fluoride treatment of osteoporosis. A simple method is described to measure the fluoride content in calcined human iliac bone samples. Bone ashes were diluted in perchloric acid, and the measurement of the bone fluoride content was performed using a specific ion electrode combined with a reference electrode. Reference values are given for bone tissue from 76 control subjects (0.08 +/- 0.05% of bone ash), from two groups of 117 and 102 untreated osteoporotic patients (0.05 +/- 0.03% and 0.08 +/- 0.05%, respectively), from 166 sodium fluoride-treated osteoporotic patients (mean bone fluoride content varying from 0.24 to 0.67%, depending on the duration of therapy), and from 96 patients showing typical skeletal fluorosis (mean bone fluoride content varying from 0.56 to 1.33%, depending on the etiology of fluorosis and the relationship with the amount of fluoride ingested as well as with the duration of fluoride exposure). During a prolonged exposure of adult bone tissue to fluoride, the early bone fluoride uptake is variable and depends on the remodeling activity; then it increases rapidly before becoming more or less stable at a maximum level.

[Contribution to the study of the treatment of osteoporosis using fluoride. Long-term sequelae following discontinuation of fluoride]. / Contribution à l'étude du traitement de l'ostéoporose par le fluor. Evolution à long terme après l'arrêt du fluor.

Eight idiopathic or postmenopausal osteoporotic patients were studied prospectively over a 4- to 6-year period of treatment with fluoride, calcium, phosphate and vitamin D. After fluoride and phosphate were discontinued they were followed up for a further 6-year period.

Rapidly progressive osteoarthrosis of ochronotic origin. A pathologic study.

A case of hip osteoarthrosis associated with ochronosis in a 65-year-old woman is reported. Characteristic features of both conditions were observed macroscopically and on light and electron microscopic examination. In the cartilage the pigment deposits were located on and between thick collagen fibrils. In the synovial membrane there were embedded packets of cartilage shards of which the collagen fibrils and pigment were phagocytosed, as well as calcified bone debris whose disaggregation might have explained the presence of some apatite deposits free of any underlying collagen structure. As also previously observed, the present case of ochronotic hip osteoarthrosis is remarkable for the minor osteophyte formation and for the inclusion of pigmented cartilage shards in the osteomedullar remodeled territory. It also demonstrates a collapse of the femoral head cortex presumably related to the rapid clinical and radiologic evolution. By the well-known origin of its chondropathy and by the pigment labeling of the cartilage, ochronotic arthropathy provides an almost experimental model for analyzing a broader problem, i.e., that of the various components of an osteoarthrotic remodeling.

Biophysical study of bone mineral in biopsies of osteoporotic patients before and after long-term treatment with fluoride.

Crystallographic characteristics of bone mineral were examined in a group of 60 osteoporotic patients before and after 3 to 6 years of fluoride therapy. The age of the mineral was evaluated by means of X-ray absorption, as degree of mineralization of bone tissue (MDBT). Crystallinity was evaluated by measuring both X-ray diffraction line broadening, beta (31.0) and beta (00.2), and the crystallinity index (CI) by infrared spectrometry. The a and c unit-cell parameters were determined by powder X-ray diffraction. Bone fluoride content was measured by specific electrode. Patients were divided in two groups according to MDBT before treatment: one group with MDBT values less than or equal to mean value; another group with MDBT values greater than mean value. In the first group, trabecular bone volume (TBV) did not change significantly during therapy. In the second group, an increase of TBV was observed. Osteoporoses can then be distinguished, on MDBT criterion, between osteoporosis with hypermaturated mineral and osteoporosis with hypomaturated mineral. The MDBT before treatment permits one to predict the effect of fluoride therapy on TBV. In the two groups there was a significant increase in bone fluoride content between the onset and the end of treatment. Bone fluoride content increased linearly during therapy without any plateau effect. Crystallographic modifications induced by fluoride explain the mechanical and chemical improvement of bone.

Ultrastructural study of the long-term development of two experimental cutaneous calcinoses (topical calciphylaxis and topical calcergy) in the rat.

Skin calcification induced by topical calciphylaxis was provoked by a subcutaneous injection of iron chloride in rats previously sensitized by dihydrotachysterol. A cutaneous topical calcergy was induced by an injection of potassium permanganate. An electron-microscopical study of the long-term evolution of both these models of calcification was made. After the initial stages, mineralization of the connective tissue continued by a secondary nucleation process without matrix vesicles. The mineral composed of needle-like structures, apatite in nature, was mainly deposited between and around collagen fibrils, and showed various arrangements in calcified plaques. Intrafibrillar calcification was rarely observed and appeared only in the later stages. The extension of calcified deposits then stopped. Finally, there was a fragmentation of the mineralized area which was progressively surrounded by uncalcified collagen fibrils. A demineralization process, caused by cells such as macrophages and multinucleated giant cells, rather than a resorption of the calcified deposits, was noted. It is important to emphasize that, in both models of ectopic calcification, an evolution toward ectopic ossification was never observed, which is perhaps due to the absence of extensive resorption mechanisms.