Bone In Young Adults Research Articles

Bilateral Brodie's Abcess on the Proximal Tibia

Brodie's abcess, a local form of subacute osteomyelitis, is a rare disease and usually occurs in the metaphysis or epiphysis of the long tubular bone in young adults. Generalized symptoms and signs resembling infectious disease are uncommon. Abnomalities in laboratory findings are not severe. Because of these characteristics and nonspecific radiology, there are difficulties in the differential diagnosis with other infectious disease and tumorous conditions. The authors experienced a case of Brodie’s abcess in the proximal tibia bilaterally.

Microscopic configurations on the bare‐bone surfaces of mammalian synovial joints

AbstractThe smoothness characteristic of synovial joint surfaces of bare bones is shown to be an illusion; low‐power microscopy of young adult human bones from interments revealed, on the surfaces of a variety of synovial joints, a system of basically hemispherical elevations, often united as short chains or groups. This system was also found on joints of a variety of species of six mammalian orders. Under the higher magnification of scanning electron microscopy (SEM), many elevations had a pit at their summits. The bare‐bone surfaces of synovial joints have a thin covering of mineralized cartilage, including its mineralizing‐front, which survives taphonomic processes, as well as the preparative procedures used in the study of articular surfaces. In its formative phase, the front has the chondrocyte–columnar structure of cartilage. It is postulated here that the newly‐discovered elevations arise when cartilage formation is ceasing, or becoming dormant, and that each column‐unit produces a globular mineralized mass, often with a pit which had accommodated a chondrocyte. These masses may incorporate the fibre systems of the unmineralized cartilage and aid in its attachment to the bony surface. Copyright © 2001 John Wiley & Sons, Ltd.

Visceral primitive peripheral neuroectodermal tumors: A clinicopathologic and molecular study

Ewing sarcoma–primitive neuroectodermal tumor (EWS/PNET) belongs to the group of pediatric small round blue cell tumors; although EWS/PNET is classically a tumor of the soft tissue or bone in children and young adults, individual cases have been described in patients of all ages. A group of chromosomal translocations involving the EWS gene and a member of the Ets transcription factor family of genes has been detected in EWS/PNET, and heterogeneity in the precise breakpoint of the translocation has been shown to generate a group of related fusion transcripts that may have prognostic significance. Within the last decade, the clinicopathologic spectrum of EWS/PNET has been markedly expanded by recognition that the tumor may also have a visceral origin. To determine whether visceral EWS/PNET has the same pattern of genetic alterations and range of fusion transcripts as EWS/PNET of bone and soft tissue, we performed reverse-transcription polymerase chain reaction–based testing of formalin-fixed, paraffin-embedded tissue from a series of visceral tumors for which the diagnosis of EWS/PNET was well established. Together with additional cases compiled from the literature, EWS-Fli1 (or a related fusion transcript) was present in 18 of 19 visceral EWS/PNET, with a distribution of transcript types not statistically different from EWS/PNET of soft tissue and bone (P >.05, X2 test). These results firmly establish the genetic relationship between EWS/PNET of visceral sites, soft tissue, and bone. HUM PATHOL 32:1109-1115. Copyright © 2001 by W.B. Saunders Company

Treatment of postmenopausal osteoporosis.

POSTMENOPAUSAL OSTEOPOROSIS IS a common and serious clinical problem. As both individuals and society have come to recognize the importance of preventing and treating osteoporosis, several new medications have been developed that have been shown to reduce fracture rates in women with osteoporosis. This article will review recent studies and evaluate the currently available treatments for osteoporosis. All women with low bone mineral density (BMD) should ingest 1200 to 1500 mg of calcium and 400 to 800 IU of vitamin D daily. The National Osteoporosis Foundation recommends pharmacological treatment of all postmenopausal women with T scores (the number of SDs below peak young adult bone mass) below −2.0, and those with T scores below −1.5 and risk factors for osteoporosis. However, for the same level of BMD, the fracture risk is much greater in older than in younger subjects. Furthermore, the greatest benefit in fracture reduction occurs in patients with preexisting vertebral fractures or T scores below −2.5. While older women with low BMD and a history of an osteoporotic fracture should be treated pharmacologically, the decision is less clear for other patients.

Peripheral Osteoporosis Screening in the Menopausal Woman Using the Calcaneus Heel Ultrasound

Objective: Ultrasound of the calcaneus heel has the potential as a non-invasive, radiation free, highly mobile and inexpensive method for screening for osteoporosis. The objective of this study was to established a database for bone mass in a general population of menopausal women using a heel ultrasound device. Design: This was a retrospective study in which data on bone density was determined in postmenopausal women using a heel ultrasound device. Osteoporosis screening was conducted in 15 selected primary care clinics at representative sites throughout the state of Nebraska during the period of December 1998 to October 1999. Materials and Methods: The Lunar Achilles+ Heel Ultrasonometer, used in this study, combines the ultrasound transmission velocity (speed of sound) and attenuation of ultrasound (broadband ultrasound attenuation) to formulate a “stiffness” value that is used in calculation of a T-Score (i.e. the standard deviation below the young adult bone mass). Data on bone mass were determined by the T-Score value. After obtaining an abbreviated patient history, either the right or left heel was evaluated by the ultrasound. The data obtained were analyzed by descriptive statistics, linear regression, Chi Square analysis and one-way analysis of variance. Results: A total of 586 menopausal women were evaluated with an age range of 33 (surgical) - 93 years of age. Independent of age, general findings indicated that 38.2% (n=224) had a normal bone mass (T-Score = <−1), 44.9% (n=263) were osteopenic (T-Score = −1 to −2.5) and 16.9% (n=99) were osteoporotic (T-Score =>−2.5). When the women were separated into age groups of less than 65 (n=257) or 65 and older (n=322), the results indicated that 54.5% had a normal bone mass, 38.9% were osteopenic and 6.6% were osteoporotic in the <65 age group, whereas in the 65 years or older group, 25.2% were normal, 49.4% were osteopenic and 25.5% were osteoporotic. The difference in the distribution of bone mass between the two age groups was highly significant (P<0.001). In the total population of menopausal women, there was a highly significant correlation (P<0.001) with age and the T-Score (i.e. as age increased the T-Score became more negative). The mean age group was 60.7±.6 years for normal bone mass, 66.3 ± .5 years for those diagnosed with osteopenia, and 72.8 ± .4 years for those diagnosed with osteoporosis (P<0.001). For all age groups, there was a significantly (P<0.001) greater proportion of women with normal bone mass (vs low bone mass) who were taking the combination of estrogen replacement therapy (ERT) and calcium supplementation (Ca) vs those who were taking ERT or Ca alone or neither one. Conclusions: (1) Ultrasound of the calcaneus heel appears to be an excellent screening tool for osteoporosis. (2) The results support other studies indicating that women 65 years or older are at high risk for osteoporosis. (3) ERT without adequate Ca does not appear to be protective against bone loss. This study was supported in part by Merck & Co., Inc.

Does bone design intend to minimize fatigue failures? A case for the affirmative.

Threshold strain ranges help to control the ability of modeling to increase bone strength and "mass" and the ability of remodeling to conserve or decrease them. Whether expressed as strains or stresses, the probable remodeling threshold of bone (MESr) lies below its modeling threshold (MESm), which lies below its operational microdamage threshold (MESp), which lies well below its ultimate strength (Fx). Given normal modeling and remodeling potentials, that arrangement should tend to cause whole-bone strength and stiffness to keep typical peak bone strains ("E") from voluntary activities from exceeding bone's modeling threshold and therefore from reaching its microdamage threshold. Satisfying that laddered "MESr < "E" < MESm << MESp <<< Fx" arrangement should minimize fatigue failures of bones, which might be at least one purpose of normal bone design. That arrangement would have practical implications that include, in part, the following. (A) It could make healthy young adult bones about six times stronger than needed for the largest voluntary loads they usually carry. (B) It suggests a biomechanical pathogenesis for different kinds of osteoporosis. (C) It suggests design criteria that load-bearing bone implants and endoprostheses should satisfy to endure their voluntary mechanical usage. (D) It also suggests features that future models of mechanical loading effects on bone strength, architecture, and "mass" might incorporate.

Recurrent anomalies of 6q25 in chondromyxoid fibroma

Chondromyxoid fibroma is a rare benign bone tumor most commonly arising in the metaphysis of long bones in young adults. Histopathologically, chondromyxoid fibroma may be difficult to distinguish from other cartilaginous neoplasms. Recently, a pericentric inversion of chromosome 6 [inv(6)(p25q13)] has been proposed as a specific genetic marker for chondromyxoid fibroma. In this study, cytogenetic and spectral karyotypic analyses of 2 chondromyxoid fibroma cases showed clonal abnormalities of chromosome 6 but at a breakpoint on the long arm (q25) distal to that described in the pericentric inversion. These findings suggest that several distinct breakpoints on chromosome 6 are nonrandomly involved in chondromyxoid fibroma.

A 73-Year-Old Woman With Osteoporosis

DR DALEY: MRS Z IS A 73-YEAR-OLD MARRIED GRANDmother who lives in a suburb of Boston, Mass, with her husband. She works 4 days per week in her daughter’s retail business. Her gynecologist recently referred her for evaluation of “thin bones.” Mrs Z has medical insurance through Medicare and supplemental insurance. Mrs Z underwent menarche at age 11 years and had normal menstrual periods until menopause at age 50 years. She had 2 uncomplicated pregnancies and took oral contraceptives for many years. After menopause, she took hormone replacement therapy (HRT) for only 3 years, then stopped because of fear of developing breast cancer. She smoked for 1 year in her teens and quit; she does not drink alcohol. She has never taken glucocorticoids, anticonvulsants, or thyroid medication. Her mother fractured her hip twice. There is no family history of breast cancer. The patient’s daily dietary calcium intake is low, about 300 mg/d, but she has taken supplemental calcium tablets of about 1200 mg/d for the past several years. She has never had a kidney stone. Mrs Z is physically active, walking almost every day. She has had multiple fractures, including a left hip fracture in 1990, a right wrist fracture when she was in her 60s, and a right elbow fracture approximately 10 years ago. She also noted that she has lost about 2 to 3 inches in height during the past several years. Her gynecologist recently obtained a bone density study of her femoral neck and total hip, the results of which were 4.69 and 5.02 SDs below young adult peak bone mass (FIGURE 1). Mrs Z has other significant conditions, including hypertension, hyperlipidemia, and coronary artery disease leading to acute myocardial infarction in 1990. She underwent coronary artery bypass grafting in 1990 and again in February 1998; with recurrent ischemic chest pain in May 1998, she had several coronary artery stents placed. In August 1998, Mrs Z underwent a right radical nephrectomy for renal cell carcinoma. She has moderate renal insufficiency, with a stable creatinine level of 203 μmol/L (2.3 mg/dL) after nephrectomy. Mrs Z’s current medications include metoprolol tartrate, atorvastatin chloride, folic acid, pyridoxine hydrochloride (vitamin B6), cyanocobalamin (vitamin B12), aspirin, vitamin E, a multivitamin supplement, and calcium carbonate. Physical examination revealed that Mrs Z was a thin woman, with a blood pressure of 140/80 mm Hg, heart rate of 80/min, weight of 43 kg (96 lb), and height of 146 cm (57.5 in); she reported an early-adulthood height of 152 cm (60 in). Her thyroid examination showed normal findings. Examination of the back showed both kyphosis and scoliosis and a recent right nephrectomy scar. Cardiac examination showed a well-healed sternotomy scar. Laboratory results, including serum albumin, calcium, parathyroidhormone(PTH), thyroid-stimulatinghormone, free thyroxine, protein electrophoresis, and immunoelectrophoresis, were normal. Alkaline phosphatase level was elevated, at 187 U/L (reference range, 40-120 U/L). 25-Hydroxyvitamin D levels were slightly elevated, at 147 nmol/L (reference range, 25-137 nmol/L). Collagen cross-linked N-telopeptide was 89 nmol of bone collagen equivalent per millimole of creatinine(premenopausal reference range,14-74nmol), avalueconsistent with the patient’s postmenopausal state. Evaluation in the osteoporosis center of Beth Israel Deaconess Medical Center, Boston, confirmed the diagnosis of postmenopausal osteoporosis (Figure 1 and FIGURE 2). Recommendations included changing Mrs Z’s calcium supplement to Caltrate Plus D (an over-the-counter preparation of calcium and vitamin D), 600 mg 2 times per day; cholecalciferol, 400 to 800 IU/d (400 IU from her multivitamin supplement and the balance from Caltrate Plus D); daily exercise (walking); alendronate sodium, 10 mg/d; and repeat bone densitometry in 1 to 2 years.

Osteoprogenitor cell frequency in rat bone marrow stromal populations: Role for heterotypic cell-cell interactions in osteoblast differentiation

Glucocorticoids, notably dexamethasone (Dex), have been reported to be a requirement for osteoprogenitor cell differentiation in young adult rat bone marrow stromal cell populations. We have reinvestigated the requirement for Dex and analyzed the frequency of osteoprogenitor cells present. Stromal cells were grown as primary or first subcultures in the presence or absence of Dex and their expression of osteogenic markers (alkaline phosphatase activity, hormone responsiveness, and matrix molecules, including type I collagen, osteopontin, bone sialoprotein, and osteocalcin), as well as their functional capacity to differentiate to form a mineralized bone nodule, were assessed. Dex increased, but was not an absolute requirement for, the expression of osteogenic markers. Bone nodule formation was plating cell density dependent and occurred under all combinations of treatment with or without Dex but was maximal when Dex was present in both the primary and secondary cultures. Dex increased CFU-F by approximately 2-fold, but increased CFU-O (osteoprogenitor cells; bone nodule forming cells) by 5- to 50-fold depending on the cell density and duration of treatment. Neither CFU-F nor CFU-O expression followed a linear relationship in limiting dilution analysis until very high cell densities were reached, suggesting cooperativity of cell types within the population and a multitarget phenomenon leading to osteoprogenitor differentiation. When a large number of nonadherent bone marrow cells or their conditioned medium was added to the stromal cells, osteoprogenitors comprised approximately 1/100 of plated adherent cells and their expression followed a linear, single-hit relationship. By contrast, rat skin fibroblasts or their conditioned medium totally inhibited bone nodule formation. These data support the hypothesis that in marrow stroma, as in other bone cell populations such as those from calvaria, there are at least two classes of osteoprogenitor cells: those differentiating in the absence of added glucocorticoid and those requiring glucocorticoid to differentiate, that more than one cell type is limiting for stromal osteoprogenitor differentiation suggesting a role for heterotypic cell-cell interactions in osteogenesis in this tissue, and that Dex may be acting directly and/or indirectly through accessory cells in the bone marrow to alter osteoprogenitor cell expression.

Sand Fiold: the Excavation of an Exceptional Cist in Orkney

Sand quarrying in 1989 at Sand Fiold, Sandwick, in Orkney resulted in the accidental discovery of a rock-cut chamber containing a cist. Subsequent excavation revealed that this cist had a number of unusual features. The cist slabs had been fitted together exceptionally well and the completed cist was designed to be re-opened by the removal of a side slab. Within the chamber, access was provided to the opening side of the cist and a relieving structure was built over its capstone.The cist contained cremation and inhumation burials that had been inserted on more than one occasion; as its builders intended. A collection of poorly preserved unburnt bone was found to comprise the remains of two individuals: a young adult and a foetus. Two collections of cremated bone, each derived from a single adult, were also present; one in a Food Vessel Urn, the second forming a pile on the floor and containing two burnt antler tines and two unburnt human teeth. The un-urned cremation deposit and the unburnt bones had been covered in mats of plant fibres derived from grass and sedge. The urn had been lined with basketry, also made from grass. Outside the cist, an exceptionally large collection of fuel ash slag (FAS), derived from a cremation pyre, had been deposited between the cist and the wall of the rock-cut chamber.Radiocarbon dates indicate that the site and its contents had a long history. The FAS and the foetus skeleton date to 2900–2500 cal BC. Between 2200 and 1900 cal BC the urned cremation and young adult human bones were inserted and charcoal was deposited in the foundation slots for the back wall of the cist. The deposition of the un-urned cremation was dated to 1000–800 cal BC, some 900 years later, when the urn had already fallen over and broken. At this time, it is assumed that the urn was restored to an upright position and propped with stones, while the stone lid for the urn was reused in the foundation slot of the left-hand side of the cist. Reuse and refurbishment over two millennia seem evidenced in the results from this cist.

The many faces of osteosarcoma.

Osteosarcoma is the most common primary malignant tumor of bone in adolescents and young adults. It accounts for approximately 15% of all primary bone tumors confirmed at biopsy. There are numerous types of primary osteosarcoma, including intramedullary (high grade, telangiectatic, low grade, small cell, osteosarcomatosis, and gnathic), surface (intracortical, parosteal, periosteal, and high-grade surface), and extraskeletal. Osteosarcoma may also occur as a secondary lesion in association with underlying benign conditions. The identification of osteoid matrix formation and aggressive characteristics usually allows prospective radiologic diagnosis of osteosarcoma. As with all bone tumors, differential diagnosis is best assessed with radiographs, whereas staging is performed with computed tomography or magnetic resonance imaging. Understanding and recognition of the variable appearances of the different varieties of osteosarcoma allow improved patient assessment and are vital for optimal clinical management including diagnosis, biopsy, staging, treatment, and follow-up.

Pulmonary eosinophilic granuloma.

A 34-year-old female smoker had had fatigue, a nonproductive cough, and fevers unresponsive to antibiotics for 3 months. In the 3 weeks before admission, she had night sweats and a weight loss of 6.8 kg. WBC count rose to 1 8,000 without a left shift. Sputum samples yielded only Candida albicans. Skin test with purified protein derivative was negative. A chest radiograph showed preservation of lung volumes with multiple bilateral nodules 1-10 mm in diameter and cysts 5-1 0 mm in diameter (Fig. 1A). A CT scan of the chest confirmed the plain film findings of nodules and small cysts (Fig. 1B). Some nodules had central lucencies. The lung bases and costophrenic angles were not involved on either side. Mediastinal and hilar adenopathy was extensive. Pulmonary function tests showed a mild restrictive abnormality. Findings on transbronchial biopsy of the right upper lobe were nonspecific, butthoracoscopic biopsy ofthe Iingula yielded the diagno515 of pulmonary eosinophilic granuloma (Figs. 1C and 1 D). Eosinophilic granuloma is a form of Langerhans cell histiocytosis that can involve lung and bone in children and young adults. Isolated lung disease is the most common finding in adults. Langerhans cell histiocytosis is characterized by an abnormal proliferation of histiocytes variably mixed with eosinophils, lymphocytes, plasma cells, and neutrophils [1]. In the lung, granulomatous inflammation occurs around bronchioles and arterioles [1]. Eosinophilic granuloma is primarily an interstitial disease, although epithelial destruction may lead to alveolar involvement. Classic radiographic findings in pulmonary eosinophilic granuloma include preserved or increased lung volumes with diffuse cysts and nodules from 1 mm to more than 1 0 mm in diameter, more common in the upper lobes and not involving the costophrenic angles [2-4]. High-resolution CT is superior to plain films for initial diagnosis, as nodules and cysts are more clearly defined [5]. Early in the disease, nodules predominate whereas cysts become more numerous later on [5]. Adenopathy is rare in adults, but it may be seen more commonly in children [2]. Spontaneous pneumothorax is identified at presentation in up to 20% of cases [2]. Pleural effusions are rare [4]. Advanced cases may be characterized by pulmonary fibrosis. Clinical and radiologic findings are often discordant [1]. Approximately 30% of patients with pulmonary eosinophilic granuloma have constitutional signs and symptoms, but up to 25% are asymptomatic [2]. The most common sign is a nonproductive cough [2]. Physical examination is often unrevealing. The disease is most common in the third and fourth decades [1]. At least 90% of cases are associated with smoking [2]. No other environmental exposures have been implicated. Results of pulmonary function tests are nonspecific and may show a mixed pattern with obstructive and restrictive components [2]. Pulmonary eosinophilic granuioma can be diagnosed with transbronchial biopsy or bronchoalveolar lavage, but definitive diagnosis often requires open or thoracoscopic lung biopsy. Patients with pulmonary eosinophilic granuloma usually have a favorable prognosis with a high rate of spontaneous remission [2, 4]. Smoking cessation is the first line of treatment; corticosteroids are added if the disease progresses. In some cases, cytotoxic drugs have been used with mixed success. Pleurodesis may be necessary for recurrent pneumothoraces.

Developmental Expression of Osteopontin (OPN) mRNA in Rat Tissues: Evidence for a Role for OPN in Bone Formation and Resorption

Osteopontin (OPN) is a 34-kDa, highly-phosphorylated glycoprotein with cell attachment properties that is a prominent constituent of the bone matrix. To aid in elucidating the function of this protein we have studied the cellular expression of OPN mRNA during the formation, growth and maturation of rat calvarial (membranous) and tibial (endochondral) bone. From Northern hybridization analysis OPN expression was demonstrated in the kidney and gravid uterus as well as in bone tissues. Compared to collagen, the expression of OPN was low in early bone formation but increased subsequently and reached peak levels in 14-day-old bone. However, both the collagen and OPN mRNAs decreased markedly thereafter and remained low in young adult bone. From in situ hybridization studies using a [35S]-labelled rat OPN cRNA probe, OPN mRNA was localized to osteoblastic cells in newly-forming calvariae, jaw bones, and in the metaphyseal and periosteal bone of the tibia. In contrast to bone sialoprotein (BSP), which is expressed almost exclusively by osteoblasts at sites of de novo bone formation, OPN transcripts were present in cells lining both endosteal and periosteal bone surfaces, and in osteocytes. Moreover, expression of OPN persisted during the subsequent growth and remodelling of both membranous and endochondral bone and was expressed at particularly high levels by bone cells and hypertrophic chondrocytes at sites of osteoclastic resorption. In the more mature bone of young adult rats OPN expression was significantly reduced but remained detectable in bone cells lining periosteal and endosteal surfaces and in the primary and secondary spongiosa of the tibia. These studies on the developmental expression of OPN support the concept of a multifunctional role for OPN in bone formation and remodelling. Thus, the expression of OPN by osteoblasts early in bone development is consistent with a role for this protein in the formation of bone matrix, whereas the peak expression of OPN later in bone development, together with high expression at sites of rapid remodelling, indicate that OPN deposited on the surface of mineralized connective tissues may provide a template for osteoclastic resorption.

Adaptations of young adult rat cortical bone to 14 days of spaceflight.

To determine whether mature humeral cortical bone would be modified significantly by an acute exposure to weightlessness, adult rats (110 days old) were subjected to 14 days of microgravity on the COSMOS 2044 biosatellite. There were no significant changes in peak force, stiffness, energy to failure, and displacement at failure in the flight rats compared with ground-based controls. Concentrations and contents of hydroxyproline, calcium, and mature stable hydroxylysylpyridinoline and lysylpyridinoline collagen cross-links remained unchanged after spaceflight. Bone lengths, cortical and endosteal areas, and regional thicknesses showed no significant differences between flight animals and ground controls. Our findings suggest that responsiveness of cortical bone to microgravity is less pronounced in adult rats than in previous spaceflight experiments in which young growing animals were used. We hypothesize that 14 days of spaceflight may not be sufficient to impact the biochemical and biomechanical properties of cortical bone in the mature rat skeleton.

Age-related differences in the effect of in vivo administration of indomethacin on hemopoietic cell lineages of the spleen and bone marrow of mice.

During 21 days of indomethacin treatment, erythroid cells in the spleens of both young adult and older mice, and in the bone marrow of young adult mice, were increased significantly early in treatment, relative to age-matched control organs, and remained high throughout treatment. During drug exposure, the numbers of myeloid cells in young adult bone marrow, but not spleen, were reduced, but in older mice these cells were elevated in both organs. Lymphoid cells in the young adult and older mouse spleens decreased and increased, respectively, during treatment, but were unchanged and decreased, respectively, in the bone marrow of young adult and older mice. Monocyte-macrophage cells in the spleen were elevated but unchanged in the bone marrow of both age groups. During 14 days of indomethacin treatment of young adult mice, the proportions of precursor cells in DNA synthesis of only the splenic erythroid lineage were increased. Thus, the major hemopoietic lineages in both the bone marrow and spleen are affected by exposure to indomethacin in a time-dependent and age-dependent manner. For all lineages studied, those of the bone marrow were least disturbed and/or were first to recover, even during continued drug exposure.

Characterization of mineral-binding 40-kDa glycoprotein extracted from young adult rabbit alveolar bone.

A forty-kilodalton (40-kDa) protein was extracted from alveolar bone of young adult rabbit with 0.5 M EDTA after extraction with 4 M GuHCl, and purified by gel-filtration, anion-exchange and hydroxyapatite columns using a high-pressure liquid chromatography system under denaturing conditions. The purified 40-kDa protein was not susceptible to bacterial collagenase and thrombin, but was cleaved by cyanogen bromide. The protein was stained blue with Stains-all. Among various lectins, concanavalin A and lentil lectin agglutinin bound to this protein, but peanut agglutinin, Ricinus communis agglutinin, phytohemagglutinin-E and wheatgerm lectin agglutinin did not. Lectin binding assays showed that the protein is a glycoprotein containing large amounts of mannose and/or glucose residues, but is not a fragment of proteoglycan. The amino acid composition of the protein shows a characteristically high content of acidic amino acids. Therefore, the mineral-binding 40-kDa glycoprotein is considered to be osteonectin/secreted protein acidic and rich in cysteine (SPARC), in terms of similarities to bovine and porcine osteonectins with regard to molecular weight and contents of glycoses and amino acids.

Production of monoclonal antibodies specific for human bone γ-carboxyglutamic acid containing protein

Murine monoclonal antibodies specific for human bone gamma-carboxyglutamic acid containing protein (BGP) were produced against BGP purified from young adult human long bones. The amino acid composition of purified protein corresponds with that of human BGP, and Western blot analysis revealed that the antibodies reacted most intensely with the cytoplasm of osteoblasts and less intensely with the cytoplasm of osteocytes, but did not react with any other cells, such as chondrocytes, or osteoclasts. Because of their ability to react with routinely processed tissue sections and their marked reactivity with human osteoblastic cells, the antibodies are expected to be a useful tool for studying the process of ossification in human bones and for the immunohistochemical diagnosis of human osteogenic tumours.

An unusual case of craniofacial fibrous dysplasia presenting in early infancy

Fibrous dysplasia (FD) of bone is one of the most frequently encountered anomalies of skeletal development. It may involve one or more bones and, particularly when polyostotic, is sometimes associated with abnormal skin pigmentation and endocrine abnormalities. FD occurs mainly in large limb bones, ribs, and craniofacial bones in older children and young adults. Usually craniofacial involvement is detected because of local swelling or asymmetry of the face or head. Neurological symptoms, primarily due to involvement of the foramina, have been reported but are not common. Infantile fibrous dysplasia of the craniofacial region has rarely been reported.

Mineralized bone nodule formation in vitro by cell populations from young adult rabbit alveolar bone.

Mineralized bone nodule formation in vitro by cell populations from young adult rabbit alveolar bone.

Bone formation in vitro by stromal cells obtained from bone marrow of young adult rats.

Cells from fetal or neonatal skeleton can synthesize bone-like tissue in vitro. In contrast, formation of bone-like tissue in vitro by cells derived from adult animals has rarely been reported and has not been achieved using cells from bone marrow. We have explored development of bone-like tissue in vitro by bone marrow stromal cells. Marrow stromal cells obtained from 40-43-day-old Wistar rats were grown in primary culture for 7 days and then subcultured for 20-30 days. Cells were cultured in either alpha-minimal essential medium containing 15% fetal bovine serum, antibiotics, and 50 micrograms/ml ascorbic acid, or the above medium supplemented with either 10 mM Na-beta-glycerophosphate, 10(-8) M dexamethasone, or a combination of both. Cultures were examined using phase-contrast microscopy, undemineralized and demineralized tissue histology, histochemistry (for alkaline phosphatase activity), immunohistochemistry (for collagen type, osteonectin, and bone Gla-protein), scanning and transmission electron microscopy, energy dispersive X-ray microanalysis, and X-ray diffraction. Collagenous, mineralized nodules exhibiting morphological and ultrastructural characteristics similar to bone were formed in the cultures, but only in the presence of both beta-glycerophosphate and dexamethasone. Cells associated with the nodules exhibited alkaline phosphatase activity. The matrix of the nodules was composed predominantly of type-I collagen and both osteonectin and Gla-protein were present. X-ray microanalysis showed the presence of Ca and P, and X-ray diffraction indicated the mineral to be hydroxyapatite. The nodules were also examined for bone morphogenetic protein-like activity. Paired diffusion chambers containing partly demineralized nodules and fetal muscle were implanted intraperitonealy in rats. Induction of cartilage in relation to muscle was observed histologically after 40 days in the chambers. This finding provided further support for the bone-like nature of the nodules. The observations show that bone-like tissue can be synthesized in vitro by cells cultured from young-adult bone marrow, provided that the medium contains both beta-glycerophosphate and, particularly, dexamethasone.