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PubMed1997

Clinical usefulness of markers of bone degradation and formation.

The evaluation and management of patients with metabolic bone disease has been enhanced in recent years by the availability and clinical application of new biochemical markers of bone degradation and bone formation. Traditionally, biochemical markers such as serum alkaline phosphatase activity and urinary hydroxyproline measurements have been used to facilitate the clinical monitoring of patients receiving therapy for metabolic bone diseases like Paget's disease and osteomalacia. The poor specificity and sensitivity of these older markers however, made it difficult to follow patient response to therapy with the more subtle bone diseases like osteoporosis and metastatic bone cancer. New advances in bone marker biology particularly with biochemical markers of bone resorption have renewed interest in the use of biochemical markers to manage patients with different forms of metabolic bone disease. Bone loss markers such as the pyridinium cross-links and associated telopeptides have expanded the application of bone markers to not only monitor therapy in patients with metabolic bone disease but to reliably predict the bone density response to anti-resorptive medications. These markers have also been used to identify patients at risk for fractures who have significant bone density loss as a result of bone disease or as a physiologic consequences of menopause. This report reviews the relevant, newer markers of bone turnover and their current clinical utility in patients with osteoporosis and metastatic bone disease.

Biomarkers↗
PubMed2003

Paraplegia-related alterations of bone density in forearm and hip in Greek patients after spinal cord injury.

PURPOSE: Paraplegia due to spinal cord injury is related with sublesional bone demineralization with an increased incidence of pathologic fractures in lower extremities. This study was carried out in order to evaluate bone density alterations in forearm and hip in Greek paraplegic patients after spinal cord injury and to correlate the findings with the level of injury, the neurological status, the time interval from injury and the performing of physiotherapy and therapeutic standing. METHOD: Fifty-seven paraplegic patients (33 men and 24 women, with injuries sustained from 6 months to 27 years) and 36 able-bodied age-matched controls (25 men, 16 women) participated in the study. Bone mineral density (BMD) was measured by dual X-ray absorptiometry (DXA) in the proximal and distal forearm, the femoral neck, the greater trochanter and Ward's triangle. RESULTS: The measurements revealed a significant reduction of BMD of femoral neck (p<0.001 in male, p<0.001 in female paraplegics), greater trochanter (p<0.001 and p=0.001, respectively) and Ward's triangle (p=0.001 and p=0.005, respectively). Proximal forearm depicted non-significantly decreased BMD values and distal forearm depicted a slight increase in BMD values. The degree of demineralization was independent of factors such as complete or incomplete spinal cord injury, level of the lesion, physiotherapy and performing of standing. In addition to that, BMD values in both hip and forearm showed no statistically significant correlation with time after injury. CONCLUSIONS: BMD measurements in Greek paraplegic patients reveal bone loss, which most dramatically occurs in the region of hip with a consequent increase of fracture risk. Forearm measurements depict a non-homogeneous response with limited proximal bone loss and slight distal increase of BMD, the latter being possibly attributed to daily activities.

Adult↗
PubMed1989

Histochemical detection of osteocalcin in normal and pathological human bone.

We investigated the immunohistochemical localization of osteocalcin in demineralized, paraffin-embedded normal and pathological human bone. Acid decalcification protocols appeared to be more suitable for osteocalcin detection than mild chelating agents. In normal lamellar bone, osteocalcin was detected in osteocytes and along the lamellar bone matrix in fine granular deposits. Under pathological conditions (osteomyelitis, neoplasia), appositional bone showed immunoreactivity in osteoblasts and osteocytes but not in the provisory woven bone matrix. Intense immunoreactivity could be seen at the cell borders of osteoclasts and the bone margins of Howship lacunae. In primary bone-forming tumors, osteocalcin immunoreactivity was detected in osteoblasts and their malignant counterparts. On the basis of these results, we conclude that optimal preservation of osteocalcin is obtained through mild acid decalcifiers. Osteocalcin is deposited in bone matrix, especially that of metabolically inactive bone. In neoplasms, osteocalcin could be a marker of osteoblastic differentiation.

Bone Neoplasms↗
PubMed1975

Osteomalacia associated with anticonvulsant drug therapy in mentally retarded children.

A survey of 289 severely retarded inpatients at a school for retarded children in American Fork; Utah revealed 67 patients with osteomalacia as defined by hypocalcemia, hypophosphatemia, elevated serum alkaline phosphatase levels, and appropriate bone changes. Investigation of the variables which might influence bone mineralization revealed no differences in age, sex, physical activity, sunshine exposure, or dietary intake of vitamin D between the osteomalacia and nonosteomalacia groups. However, all of the patients with osteomalacia were receiving anticonvulsant medications, either phenobarbital, diphenylhydantoin, or both. Duration of anticonvulsant therapy was the most important contributing factor to the development of osteomalacia. Seventy-five percent of patients who had received anticonvulsants for more than ten years had osteomalacia. The single most costly medical problem at the school is the treatment of pathologic bone fractures due to demineralized bone.

Adolescent↗
PubMed1997

The clinical spectrum of chronic metabolic acidosis: homeostatic mechanisms produce significant morbidity.

Chronic metabolic acidosis is a process whereby an excess nonvolatile acid load is chronically placed on the body due to excess acid generation or diminished acid removal by normal homeostatic mechanisms. Two common, often-overlooked clinical conditions associated with chronic metabolic acidosis are aging and excessive meat ingestion. Because the body's homeostatic response to these pathologic processes is very efficient, the serum HCO3- and blood pH are frequently maintained within the "normal" range. Nevertheless, these homeostatic responses engender pathologic consequences, such as nephrolithiasis, bone demineralization, muscle protein breakdown, and renal growth. Based on this, the concept of eubicarbonatemic metabolic acidosis is introduced. Even in patients with a normal serum HCO3- and blood pH, it is important to treat the acid load and prevent pathologic homeostatic responses. These homeostatic responses, as well as the mechanisms responsible for their initiation, are reviewed.

Acid-Base Equilibrium↗
PubMed2004

In situ expression of RANKL, RANK, osteoprotegerin and cytokines in osteoclasts of rat periodontal tissue.

OBJECTIVES: This study examined the in situ expression of receptor activator of nuclear factor-kappaB ligand (RANKL), receptor activator of nuclear factor-kappaB (RANK), osteoprotegerin, interleukin-1beta (IL-1beta) and tumor necrosis factor alpha (TNFalpha) in the osteoclasts of rat periodontal tissue. BACKGROUND: In periodontal disease, osteoclasts cause resorption of the alveolar bone. The function of osteoclasts is regulated by interaction with periodontal ligament cells (PDLs). Furthermore, various kinds of molecules such as RANKL, RANK, osteoprotegerin, IL-1beta and TNFalpha are known to be related to the osteoclasts differentiation and function. It is therefore important to observe the expression of RANKL, RANK, osteoprotegerin and cytokines in osteoclasts and PDLs. METHODS: Four-week-old Wistar rats were used. Tooth movement was performed by the Waldo method, and the pathological bone resorption was induced. The demineralized maxillae and mandiblae were embedded with paraffin. In situ hybridization was performed to detect RANKL, RANK, osteoprotegerin, IL-1beta, and TNFalpha mRNAs in osteoclasts and other cells using the specific RNA probes, respectively. RESULTS: Both RANKL and RANK were concomitantly expressed in some osteoclasts. RANKL was also positive in osteoblasts and PDLs. No IL-1beta- and TNFalpha-positive osteoclast was noted. The positive signals of osteoprotegerin were detected in almost all osteoblasts, PDLs and odontoblasts. No osteoprotegerin-positive osteoclasts were observed. The number and the distribution pattern of RANKL- and RANK-expressing osteoclasts changed when orthodontic excessive force was applied to periodontal tissue. In addition, IL-1beta and TNFalpha were shown to be expressed in osteoclasts under pathological status. CONCLUSION: These findings suggest that an autocrine mechanism of RANKL-RANK exists in osteoclast, which is heightened in the pathological conditions. Furthermore, the autocrine mechanism of IL-1beta and TNFalpha is also provided in osteoclast under pathological condition. These autocrine mechanisms therefore seem to regulate the osteoclast function in both physiological and pathological conditions.

Animals↗
PubMed1993

Utilization of microgravity bioreactors for differentiation of mammalian skeletal tissue.

Bioreactor cell and tissue culture vessels can be used to study bone development in a simulated microgravity environment. These vessels will also provide an advantageous, low maintenance culture system on space station Freedom. Although many types of cells and tissues can potentially utilize this system, our particular interest is in developing bone tissue. We have characterized an organ culture system utilizing embryonic mouse pre-metatarsal mesenchyme, documenting morphogenesis and differentiation as cartilage rods are formed, with subsequent terminal chondrocyte differentiation to hypertrophied cells. Further development to form bone tissue is achieved by supplementation of the culture medium. Research using pre-metatarsal tissue, combined with the bioreactor culture hardware, could give insight into the advantages and/or disadvantages of conditions experienced in microgravity. Studies such as these have the potential to enhance understanding of bone development and adult bone physiology, and may help define the processes of bone demineralization experienced in space and in pathological conditions here on earth.

Animals↗
PubMed1989

Locomotor consequences of electrical and radiation injuries, burns and freezings.

Damage to bones and/or joints caused by occupational exposure to electrical current, heat, cold, and ionizing radiations remains a relatively little known entity among rheumatologists. Radiologically only a few typical changes may be seen. Bone demineralization, reflex dystrophy, periostitis, osteomyelitis, osteonecrosis, pathological fractures, degenerative joint disease and, in radiation-induced damage, malignancies, do not differ from those occurring from other causes or arising spontaneously. Correct interpretation of the radiological changes often rests on a history of past exposure. Because of the time lapse between exposure and evidence of damage, patients frequently omit to inform their doctors. Only by taking a careful history and elucidating such exposure can a proper diagnosis be made.

Burns↗
PubMed1998

Interactions among iron, calcium, phosphorus and magnesium in the nutritionally iron-deficient rat.

We studied the development of nutritional iron deficiency 0, 10, 20, 30 and 40 days after the intake of a semisynthetic diet lacking iron (diet 0) and the possible interactions with calcium, phosphorus and magnesium in both control rats and rats after 40 days of iron deficiency. During this period, iron deficiency was found to produce stress in the rats, as evidenced by high levels of cortisol in the serum. High levels of parathyroid hormone (PTH) were also found. There was a considerable increase in the absorption of calcium, phosphorus and magnesium, but the phosphorus and magnesium balance decreased and that of calcium remained practically unchanged, although there was an increase in calcium urinary elimination. Despite the noticeable degree of bone demineralization, which was evident in the femur, serum levels of calcium, phosphorus and magnesium remained constant. The present study shows that severe nutritional ferropenic anaemia provokes significant alterations in the metabolism of calcium, phosphorus and magnesium. We conclude that these alterations should be taken into account in the treatment of this pathology, given its prevalence and the fact that it may exacerbate other pathologies, particularly those related to the metabolism of calcium and phosphorus.

Anemia, Iron-Deficiency↗
PubMed1985

Histologic evaluation of new attachment in humans. A preliminary report.

This study was designed to evaluate the potential for regeneration of a new attachment (alveolar bone, cementum and a functional periodontal ligament) in patients whose attachment apparatus had been destroyed by periodontal disease. In each of the three parts of the investigation, the most apical level of calculus on the root served as a histologic reference point to measure regeneration. In Part I, attempts were made to initiate the formation of a new attachment by surgical debridement, crown removal (coronectomy) and submersion of the vital root below the mucosa. Nonsubmerged, surgically debrided defects served as controls. In Part II, debrided intrabony defects were treated with and without demineralized freeze-dried bone allograft and the associated vital roots were submerged. Part III evaluated potential for regeneration of a new attachment in nonsubmerged roots with and without the use of demineralized freeze-dried bone allograft. Gingival grafts were placed over the experimental and control sites in an attempt to retard epithelial migration. Biopsies were obtained in 6 months and regeneration was evaluated histometrically. Preliminary results in 7 patients and 24 intrabony defects indicate that new attachment is possible on pathologically exposed root surfaces in a submerged environment with and without the incorporation of demineralized freeze-dried bone allografts. New attachment was observed on pathologically exposed root surfaces in a nonsubmerged environment when intrabony defects were grafted with demineralized freeze-dried bone allograft. New attachment was not observed on nongrafted, nonsubmerged, defects with and without the placement of gingival grafts over the defects.

Alveolar Process↗
PubMedDate not supplied

The influence of age, height, and weight on the bone mineral content of lumbar vertebrae.

The bone mineral content of 109 excised lumbar vertebrae from 21 female subjects (aged 34 to 74 years) and 15 male subjects (aged 31 to 79 years) was determined with dual photon absorptiometry. It was correlated with the age, height, and weight of the subjects and with the body weight above each vertebra. No correlation was found between the bone mineral content and the lumbar spine score of Barnett and Nordin. The bone mineral content determined with dual photon absorptiometry was also correlated with the weight of fresh and ashed bone cubes removed from the interior of 40 of the aforementioned vertebrae selected at random. The bone mineral content decreased with increasing age and at a similar rate within the ages studied in both sexes. The findings indicated that pathologic demineralization in the elderly could be the result of low bone mineral content early in life, and more frequently so in female vertebrae.

Adult↗
PubMed2006

Implantation of human demineralized bone matrix (DBM) for the treatment of juvenile bone cysts.

OBJECTIVE: Definitive bony consolidation in juvenile bone cysts. Prevention of pathologic fractures. Preservation of limb function. INDICATIONS: Juvenile bone cysts at all sites. CONTRAINDICATIONS: Malignant cystic lesions. SURGICAL TECHNIQUE: After opening and curettage, the cyst is packed with human demineralized bone matrix (DBM). POSTOPERATIVE MANAGEMENT: Clinical and radiologic checks after 1, 4, and 6 months, followed by further 6-monthly checks. RESULTS: Over a period of 2 years, nine cysts packed with DBM showed almost totally osteodense images after an average of 8 months, with no other significant changes (follow-up period: 24 months). A typical decrease in cyst transparency on the plain radiographs was already detectable in all patients after 3-4 months. Marked cortical remodeling was visible after 6 months. A significant complication in one cyst in the distal tibial region was a pathologic fracture following distortion trauma; this occurred after 5 months, probably because of insufficient filling of the cyst. The fractured limb was immobilized in a lower-leg cast and healed sufficiently for stable weight bearing after 12 weeks.

Adolescent↗
PubMed1998

Osseous regeneration in the jaws using demineralized allogenic bone implants.

Osseous defects of the jaws following trauma, congenital deformity or pathology may show poor osteogenesis and the affected area may never be completely replaced by bone or will show alveolar height loss. The purpose of the present study was to evaluate the effect of allogenic bone implants (ABI) on the osteogenesis of jaw defects. Fifty-two patients (27 males, 25 females) with cystic lesions of the jaws were randomly divided into two groups: Group A underwent enucleation and packing with adsorbable gelatine sponge. Group B underwent enucleation and grafting with ABI. Both groups were evaluated radiographically. The height of the alveolar process was measured directly on the radiography. The density was measured with a digital densitometer. In Group A, the mandibular height at 6, 12 and 24 months postoperatively was 88%, 80% and 78% of the preoperative heights, respectively. In Group B, the heights were 95%, 93% and 90%, respectively. These differences were significant (P < 0.05-0.01). The density in Group B was significantly greater (P < 0.05-0.01) than in Group A at 6 and 12 months postoperatively. The difference at 24 months was not significant. On the basis of these findings, it can be concluded that ABI grafting of jaw defects enhances osteogenesis and prevents alveolar height loss in the mandible. ABI represent an encouraging alternative to autogenous bone grafting.

Adolescent↗
PubMed1988

[Use of demineralized allogeneic bone transplants for plastic surgery of osteomyelitic cavities].

Plasty of osteomyelitic cavities with demineralized bone transplants was performed in 55 patients. Different methods of the bone cavity plasty were used with regard for the state of soft tissues surrounding the pathological focus, changes in the purulent focus. In most of the patients (41) the cavity was filled up with the demineralized bone transplant formed with special reference to the size of the bone wound. In the other 14 patients with false joints complicated by osteomyelitis the bone allotransplant was put in the area of the defect as a duplicator. Good results were obtained in 53 (96.4%) patients.

Adult↗
PubMed1985

"Adult T-cell leukemia/lymphoma" with bone demineralization.

Two patients with T-cell malignancy having radiographic manifestations of generalized and localized bone demineralization are reported. One, a 53-year-old man, had marked osteoporosis and severe hypercalcemia, but no clinical evidence of leukemia throughout his illness. At autopsy there was no definite evidence of bone involvement. Histologic proof was obtained from abdominal skin which revealed "adult T-cell leukemia/lymphoma (ATLL)." The second case, a 33-year-old man, complained of arthralgia in his hands and feet; radiographs showed severe localized demineralization and pathologic fractures. Specimens of his peripheral blood, cervical lymph nodes, and bone marrow revealed ATLL cells.

Adult↗
PubMed1998

Metabolic bone disease in gut diseases.

A wide spectrum of gastrointestinal illnesses impairs bone health and can result in bone pain, demineralization, and fracture. This article summarizes current knowledge of the skeletal pathology exhibited in patients with diseases of the liver, biliary tree, pancreas, and bowel. Mechanisms responsible for these syndromes and treatment options are discussed. This article enhances the practicing gastroenterologist's knowledge of the implications of gastrointestinal illness for bone.

Bone Diseases, Metabolic↗
PubMed1997

A quantitative assessment of osteoinductivity of human demineralized bone matrix.

Demineralized bone matrix (DBM) is widely used in the repair of pathologies associated with skeletal defects and periodontal diseases. The present study was directed at establishing in vivo and in vitro models for a quantitative assessment of the osteoinductivity of DBM before clinical use. Athymic mice were used in an in vivo assay to overcome the species limitations (for human DBM) found in xenogeneic animal models. Calcium contents of explants, as an indicator of new bone formation, were assayed and expressed as a change in the weight percent calcium in the explant as compared to the weight percent of calcium in the implanted material. A total of 82 mice (2 implants per mouse) were used in this study. Significant amounts of new bone were induced in this animal model in response to implantation of DBM. Muscular implantation was found to be more osteoinductive (increases of 10.0 +/- 0.4 calcium weight percent of explant) than subcutaneous implantation (increases of 1.62 +/- 0.27 calcium weight percent of explant) and new bone formation in muscular implantation sites of athymic mice mimics endochondral bone formation. Between weeks 1 to 4, the weight of explanted materials did not significantly differ from the weight of the implanted material; however, by week 5 the explant weight began to increase. Calcium deposition over the 5 weeks of implantation increased in a nearly linear fashion. Consequently week 4 was chosen as the optimum time for explantation in the in vivo assay in that sufficient calcium levels had been achieved without a significant increase in explant dry weight. Aliquots of 10, 20, 30, and 40 mg per implantation site were used in dose response studies in the in vivo bioassay. Dose response curves with DBM exhibited maximal activity at the 20 mg DBM implant dose in the in vivo bioassay. An in vitro bioassay was also developed where human periosteal (HPO) cells were chosen because osteoprogenitor cells found in bone repair typically come from periosteal tissue. Alkaline phosphatase (ALP) activity in confluent cell cultures of HPO cells exposed to DBM, as an indicator of osteoblast induction, reached its highest level on day 5 of DBM treatment. Aliquots of 2, 5, 10, 20, 30, and 40 mg DBM per flask were chosen in dose response studies using the in vitro bioassay. These dose response studies with DBM revealed that quantities approximating 5 to 10 mg DBM in the in vitro model provided for maximal levels of ALP in cell extracts. A linear correlation (R2 = 0.7397) was demonstrated between the in vivo calcium remineralization assay and the in vitro ALP assay of osteoinductivity of DBM, suggesting that the in vitro assay can be used to quantitatively assess the osteoinductive potential of DBM where production and distribution of clinically usable DBM dictates rapid analysis.

Adult↗