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PubMed1984

Uptake of Pb by human skeleton and comparative metabolism of Pb and alkaline earth elements.

Measurements of the retention of 47Ca and of 203Pb were made following their administration by intravenous injection. Translocation to bone was measured by gamma counting the feet of subjects. Uptake by bone of 203Pb was comparatively slow and extrapolation to the whole skeleton indicated that 20% of the dose had been taken up within 20 days. By time, a similar fraction of the dose had been excreted in urine. These results are consistent with Kehoe's (Ke61) long-term balance studies on 2 human subjects given stable Pb orally. Uptake by bone of 47Ca was about 1.5-2 times the amount excreted in urine. Both the uptake by bone, and its excretion in urine, were more rapid than that of 203Pb due to the greater attachment of the latter to red blood cells. However, the plasma clearance rate for Pb, like that of Sr, was greater than that of Ca.

Adult↗
PubMed1987

Actinide distribution in the human skeleton.

Radiochemical analysis of two half skeletons donated to the United States Transuranium Registry from individuals with occupationally incurred depositions, one of 241Am and the other of 239Pu, revealed an inverse proportionality between the concentration of actinide in the bone ash and the fraction of ash (or the calcium content of the ash). A similar relationship was observed in a third case suffering from osteoporosis, but the slope was shallower. These results suggest that accurate estimates of the total skeletal content of actinide can be made from radiochemical analysis of only a few bone samples.

Americium↗
PubMed1987

Macro-distribution of naturally occurring alpha-emitting isotopes of U in the human skeleton.

Argonne National Laboratory (ANL) exhumed the remains of two individuals who had received Pu by intravenous injection, performed Pu analysis on these remains, and then sent portions of individual bones to our laboratory. We analyzed these bone samples to determine the macro-distribution of naturally occurring alpha-emitting isotopes of U (234U and 238U). We found that the sacrum contained the highest concentrations of 234U and 238U (4.9 +/- 0.3 mBq g-1 of bone ash). Different ribs contained varying concentrations of 234U and 238U ranging from 0.26 +/- 0.2 to 1.6 +/- 0.4 mBq g-1 of bone ash for 234U, and from 0.16 +/- 0.1 to 1.5 +/- 0.4 mBq g-1 ash for 238U. The upper and lower values differ significantly at p = 0.001. Concentrations of 234U and 238U in vertebral bodies were lower than in left ribs numbers 1 and 2, but were similar to the concentrations in the other left ribs. The concentration of 235U was below the detection limit in each bone (lower limit of detection (LLD) = 4 X 10(-4) Bq per sample). The results indicate that the distribution of U isotopes is not uniform throughout the skeleton. Thus, the skeletal burden of U estimated from determinations in an individual bone sample may be quite erroneous until the fraction of total skeletal U contained in each bone is known.

Adolescent↗
PubMed1997

Labels of surface-seeking radionuclides in the human skeleton.

A biokinetic model of the distribution and generation of skeletal labels of 239Pu in the human body is presented. The model is based on available information on the microdistribution of transuranics elements in animals and humans. It also makes use of morphometric and histomorphometric data characterizing the human skeleton and its turnover. The model correctly describes essential features of the microdistribution established from autoradiographic analyses. Calculated concentrations of skeletal labels of 239Pu are in good agreement with measurements from a human injection case.

Animals↗
PubMed2000

Fracture occurrence from radionuclides in the skeleton.

Because skeletal fractures were an important finding among persons contaminated with 226Ra, experience with fractures among dogs in our colony was summarized to determine the projected significance for persons contaminated with bone-seeking radionuclides. Comparison by Fisher's Exact Test of lifetime fracture occurrence in the skeletons of beagles injected as young adults suggested that for animals given 226Ra, 228Ra, 228Th, or 239Pu citrate, there was probably an excess over controls in fractures of the ribs, leg bones, spinous processes, and pelvis (os coxae) plus the mandible for dogs given 226Ra and the scapulae for dogs given 228Ra or 228Th. Regression analysis indicated that significantly elevated fracture occurrence was especially notable at the higher radiation doses, at about 50 Gy average skeletal dose for 239Pu, 140 Gy for 226Ra, about 40 Gy for 228Ra, and more than 15 Gy for 228Th. The average number of fractures per dog was significantly elevated over that noted in controls for the highest radiation doses of 239Pu and 226Ra and for the higher doses of 228Ra and 228Th. For those dogs given 90Sr citrate, there was virtually no important difference from control beagles not given radionuclides, even at group mean cumulative skeletal radiation doses up to 101 Gy. Because of a large proportion of dogs with fractures that died with bone malignancy (even at dosage levels lower than those exhibiting an excess average number of fractures per dog), we conclude that fracture would not be an important endpoint at lower levels of plutonium contamination in humans such as would be expected to occur from occupational or environmental exposure.

Animals↗
PubMed1989

Bone densitometry of the peripheral skeleton with a new photon counting and imaging device.

We present a new method for the assessment of bone mineral content of the peripheral skeleton. The method employs a new photon counting and imaging area device, the multi-wire proportional counter. The system can work as a single photon absorptiometer at the energies of both I-125 and Gd-153. It can work also as a dual photon absorptiometer using one of the two pairs of isotopes (I-125, Gd-153) or (I-125, Am-241). Both the calcaneus and the forearm can be imaged in a few minutes, with either single or dual photon absorptiometry. To test this new method in a clinical environment we compared it with the standard dual photon absorptiometry of the forearm. The data collected in a cross-sectional study of bone mineral content and bone mineral density in a group of 76 patients show a good correlation between the two measurement techniques (r = 0.931). The multi-wire proportional counter, due to its imaging capabilities, has a much lower repositioning error. This allows its use in regions with a large gradient of bone mineral density, such as the calcaneus or the very distal site of the forearm, which recent data have indicated to be superior to more proximal measurements in identifying osteoporosis.

Absorptiometry, Photon↗
PubMed1997

Long-term effects of bisphosphonates on the growing skeleton. Studies of young patients with severe osteoporosis.

Osteoporosis in children and adolescents is relatively uncommon and usually secondary to identifiable causal factors. There are no generally accepted therapies for patients with no treatable underlying cause of disease. Any treatment of young patients with bone-acting compounds should be not only effective but also devoid of adverse effects on bone growth and remodeling. For many years we have been studying the effects of bisphosphonates-an effective treatment of postmenopausal osteoporosis-on the growing skeleton. We review here our experience in the treatment of young patients with osteoporosis with special emphasis on issues of skeletal safety and effectiveness, and we discuss the available literature data. We studied 12 patients aged between 10.7 and 17.2 years with symptomatic osteoporosis and multiple fractures treated with the bisphosphonates pamidronate or olpadronate for periods between 2 and 8 years continuously. Linear growth continued normally on treatment; there was even a catch-up growth in prepubertal patients, and there was no excessive suppression of bone remodeling, assessed biochemically. Bone biopsies obtained at various stages during treatment showed bone of normal lamellar structure without mineralization defects. There was an increase in calcium balance, already evident within 10 days, the level of which was maintained for at least 3 years of treatment. This was associated with progressive increases in bone mineral density along a different slope from that of healthy peers as well as correction of vertebral deformities on X-rays in patients given bisphosphonates before puberty. Treatment was well tolerated and clinical improvement was remarkable. Our studies, supported by literature data, strongly suggest that bisphosphonate therapy can be beneficial to young patients with osteoporosis for whom no other options are currently available, and justify planning controlled studies in more common conditions for which no treatment is currently available, such as osteogenesis imperfecta.

Adolescent↗
PubMed1990

The biologic behavior of hydroxyapatite implanted into the maxillofacial skeleton.

Eleven patients who previously had undergone elective facial osteotomy and in whom blocks of porous hydroxyapatite were implanted into osteotomy gaps later consented to open biopsy of the implant material. A total of 24 biopsies were harvested at a mean time of 10.2 months following implantation. Gross anatomic findings were recorded at the time of biopsy. Specimens were harvested from the zygomatic buttress of the maxilla (12), the piriform buttress of the maxilla (4), the maxillary interdental premolar region (2), and the anterior mandible (6). Histologic sections were examined undecalcified using a modified trichrome stain. Eight of the 11 patients were followed radiographically for a minimum of 24 months. In the absence of infection, there was rapid fibrovascular ingrowth and, provided there was contact with host bone, bone ingrowth. This was observed in 21 of 24 biopsy specimens. The extent of bone ingrowth, as judged qualitatively, was highly variable and did not correlate with the time interval from implantation, anatomic site, or surface area of bone-implant interface. A healing process involving an osteoid phase of bone maturation and suggestive of continued net bone production was consistently found. The gross anatomic, radiographic, and histologic findings are discussed and provide further insight into the biologic behavior of porous block hydroxyapatite implanted into the maxillofacial skeleton.

Adolescent↗
PubMed1995

Functional soft-tissue coverage in skeletonizing injuries of the upper extremity using the ipsilateral latissimus dorsi myocutaneous flap.

The concept of early "functional" soft-tissue coverage is demonstrated in three cases of severe skeletonizing avulsion/contusion injuries of the upper extremity, including the replantation of a "frozen" arm. According to the MESS score, all extremities would have been allocated to the amputation group. Therapeutic strategy consisted of primary repair of all neurovascular structures, serial debridements, and early definitive coverage with simultaneous restoration of the elbow flexor or extensor muscles. Flap survival was 100 percent in all patients, and the muscle strength achieved after vigorous physical therapy was rated M3 to M5. One patient was even able to return to competitive tennis.

Adolescent↗
PubMed1996

Langerhans cell histiocytosis: an uncommon disease commonly manifesting in the craniofacial skeleton.

Langerhans cell histiocytosis is an infrequent and enigmatic proliferative disorder that commonly presents in the head and neck region. This is an analysis of 77 patients with Langerhans cell histiocytosis treated at Children's Hospital and Dana Farber Cancer Institute from 1974 through 1993. The study focused on clinical findings, anatomic location and extent of disease, therapy, and outcome. The patients were, on average, under 5 years of age at initial presentation. Over 62 percent of the patients had signs and symptoms referred to the craniofacial skeleton. Osteolytic lesions of the cranium were the most common, followed, in frequency, by scalp rash, osteolytic mandibular tumor(s), enlarged nodes, and gingival swelling or ulceration. Single bony lesions usually were treated with curettage or radiotherapy. Chemotherapy was used commonly for advanced disease with multifocal or disseminated presentation. Initial therapy included moderate doses of single agents; other agents were added if no response was achieved. The natural history of Langerhans cell histiocytosis varied from an acute fulminant course, a waxing and waning chronic disease, to spontaneous regression. Young age at presentation and organ dysfunction predicted a poor prognosis. Statistical analysis showed that there was no significant relationship between outcome and extent of skeletal involvement when controlling for age or organ dysfunction.

Bone Diseases↗
PubMed1998

Volume maintenance of onlay bone grafts in the craniofacial skeleton: micro-architecture versus embryologic origin.

The superior volume maintenance of membranous over endochondral bone has been shown in several studies and provides the basis for its preferred clinical use as an onlay grafting material in the craniofacial skeleton. The scientific rationale for this seeming embryologic advantage, however, has never been proven. Our hypothesis is that the pattern of onlay bone graft resorption is primarily determined by a graft's micro-architecture (relative cortical and cancellous composition) rather than its embryologic origin (membranous versus endochondral). Twenty-five adult New Zealand, White rabbits were used for this study. Eight animals were killed at 3 weeks, eight animals at 8 weeks, and nine animals at 16 weeks. Three graft types were placed onto each rabbit cranium: cortical bone graft of membranous origin and cortical and cancellous bone graft of endochondral origin. Fluorochrome markers were injected into all living rabbits at 1, 6, and 14 weeks. Microcomputed tomography scanning was performed on all of the bone grafts to determine postsacrifice volumes and to obtain detailed information regarding the bone graft's trabecular architecture. In addition, specimens were examined histologically. Volume analysis showed a statistically greater resorption rate in the cancellous endochondral bone graft than in either the endochondral or membranous cortical bone grafts (p < 0.05) for all time points. In addition there was no significant difference in the resorption rates between the endochondral and membranous cortical bone grafts. A post-test power analysis (alpha = 5 percent) of the volume data comparing the two types of cortical bone grafts showed that a difference in resorption of 8.9 percent would be detected with a 90-percent probability. Previous studies, which have shown a seeming superiority of membranous over endochondral bone grafts, used composite grafts composed of both cortical and cancellous portions. By separating these components, we have shown that cortical bone grafts maintain their volumes significantly better than cancellous bone grafts. In addition, we found no statistical difference in the resorption rates between the two cortical onlay bone grafts of different embryologic origins, a finding that has never been previously published. From our results, we believe cortical bone to be a superior onlay grafting material, independent of its embryologic origin. We believe these results challenge the currently accepted theories of bone graft dynamics and may lead to a change in the way clinicians approach bone graft selections for craniofacial surgery.

Animals↗
PubMed1999

Properties of coralline hydroxyapatite and expanded polytetrafluoroethylene membrane in the immature craniofacial skeleton.

Although extensive research regarding the treatment of calvarial defects has been done in adult models, little is known about the response in the maturing skeleton. The role of coralline hydroxyapatite and expanded polytetrafluoroethylene membrane in augmenting bone growth and repair of calvarial defects in a neonatal model is explored. Utilizing a 3-week-old neonatal swine model, bone growth into 28 calvarial defects was measured. After exposure of the calvaria in seven animals, four defects of 10 mm in diameter were created. In each animal, one defect was treated with a 10-mm disc of porous hydroxyapatite alone (Interpore 500, Interpore International), and a second defect was covered with an expanded polytetrafluoroethylene membrane (Gore-Tex OV-6) secured by four 3-mm microscrews (Luhr Microsystem, Howe-Medica Inc.). The third defect combined an implanted hydroxyapatite disc covered by an expanded polytetrafluoroethylene membrane, whereas the fourth defect served as an untreated control. Histology and histomorphometry were performed on undecalcified specimens harvested at 6 weeks after surgery. In both hydroxyapatite groups, the bone growth into the inorganic matrix provided complete osseous union in all specimens, and the amount of fibrosis was significantly lower (p < 0.02) in comparison with the control. Unexpectedly, there was significant osteoclastic resorption of the hydroxyapatite matrix (35.1 percent decrease) with simultaneous bone deposition and remodeling. The addition of an expanded polytetrafluoroethylene membrane covering the hydroxyapatite implant provided an insignificant advantage in bone growth (27.3 percent versus 28.3 percent, respectively). Finally, the expanded polytetrafluoroethylene membrane alone afforded no qualitative advantage secondary to intrusion of brain and dura into the defect as well as displacement of the membrane inward during appositional growth, leading to incomplete healing of the defect with thinning of the surrounding cranial bone. Unique in this maturing model was morphologic evidence of complete union at the calvaria-hydroxyapatite interface in all specimens as well as active remodeling of the hydroxyapatite matrix. The results of this study suggest that porous hydroxyapatite may be a suitable bone substitute in maturing calvarial bone defects, achieving superior osseous integration and volumetric bone gain while undergoing concurrent resorption and remodeling.

Animals↗
PubMed2001

Distraction osteogenesis of the craniofacial skeleton.

Distraction osteogenesis is becoming the treatment of choice for the surgical correction of hypoplasias of the craniofacial skeleton. Its principle is based on the studies of Ilizarov, who showed that osteogenesis can be induced if bone is expanded (distracted) along its long axis at the rate of 1 mm per day. This process induces new bone formation along the vector of pull without requiring the use of a bone graft. The technique also provides the added benefit of expanding the overlying soft tissues, which are frequently deficient in these patients. This article reviews the authors' 11-year clinical and research experience with mandibular distraction osteogenesis. It highlights the indications and contraindications of the technique and emphasizes the critical role that basic science research has played in its evolution.

Aging↗
PubMed1990

Primary tumors of the axial skeleton. Experience of the Leeds Regional Bone Tumor Registry.

Primary tumors of the axial skeleton are rare and a survey of the Leeds Regional Bone Tumor Registry found them to constitute only 55 of the 1950 cases (2.8%). Chordoma was the most frequent tumor in the cervical and sacral regions as well as the most common diagnosis overall and osteosarcoma ranked second. Pain was the most frequent presenting symptom but over half the patients developed some neurological abnormality. In spite of treatment survival was poor in patients with malignant lesions or neurological involvement. The establishment of Bone Tumor Registries is the only way that sufficient data on large numbers of these rare tumours can be amassed to provide a valuable and otherwise unavailable source of information for research, education and service.

Adolescent↗
PubMed1995

Incomplete spondylolysis and healing. A study of ancient Canadian Eskimo skeletons.

STUDY DESIGN: Skeletons of ancient Canadian Eskimos subjected to arctic weathering presented an unusual opportunity for direct observation of all stages of spondylolysis. OBJECTIVE: To explore early stages of incomplete lysis, a phenomenon difficult to observe radiographically. SUMMARY OF BACKGROUND DATA: Although lumbar spondylolysis most often appears to be a stress fracture that may proceed to complete separation, its early stages have been difficult to visualize. METHODS: Vertebrae were examined for even minute lytic defects in the general region of pars interarticularis and the results were correlated with age at death. RESULTS: Spondylolysis was found in 51 individuals, with 110 separate sites (sides) affected. At 34 of these sites, all but two in adolescents or young adults, the lysis was incomplete. Incomplete lysis affected the superior margin of the neural arch more often than the inferior margin, and the right side more often than the left. CONCLUSION: Spondylolysis first became recognizable as incomplete stress fractures during adolescence, with most progressing to complete lysis in young adulthood. New fractures continued to develop in young adults, but most healed by middle adulthood. After 45 years of age, the overall frequency of spondylolysis declined, indicating that even complete defects occasionally healed.

Canada↗
PubMed2000

A syndrome with midface asymmetry, defective modelling of the skeleton, catch-up growth and truncal obesity.

We report follow-up from birth up to 16 years of age of a patient with a previously undescribed combination of dysmorphic features. These include: intrauterine growth retardation developing to normal adult stature with truncal obesity, asymmetry of the midface skeleton with severe orthodontic problems, brachydactyly of the hands and feet, wide medial phalanges of the fingers, partial soft tissue syndactyly, simian creases and normal mental development. We consider other differential diagnoses and suggest that the patient represents a hitherto undescribed syndrome.

Abnormalities, Multiple↗
PubMedDate not supplied

Space flight and the skeleton: lessons for the earthbound.

Loss of bone during extended space flight has long been a concern that could limit the ability of humans to explore the universe. Surprisingly, the available data do not support the concept that weightlessness leads inexorably to a depleted skeleton unable to withstand the stress of a return to a 1-g environment. Nevertheless, some bone loss does occur, especially in those bones most stressed by gravity prior to flight, which provides confirmation of the proposal formulated over a century ago by Julius Wolff that mechanical stress determines the form and function of bone. Although the phenomenon of bone loss with skeletal unloading, whether by space flight or immobilization or just taking a load off your feet (literally) is well established, the mechanisms by which bone senses load and adjusts to it are not so clear. What actually is the stimulus, and what are the sensors? What are the target cells? How do the sensors communicate the message into the cells, and by what pathways do the cells respond? What is the role of endocrine, factors vs. paracrine or autocrine factors in mediating or modulating the response? None of these questions has been answered with certainty, but, as will become apparent in this review, we have some clues directing us to the answers. Although the focus of this review concerns space flight, it seems highly likely that the mechanisms mediating the transmission of mechanical load to changes in bone formation and resorption apply equally well to all forms of disuse osteoporosis and are likely to be the same mechanisms affected by other etiologies of osteoporosis.

Animals↗
PubMed2005

Mandibular growth following reconstruction using a free fibula graft in the pediatric facial skeleton.

BACKGROUND: Mandible reconstruction in the growing facial skeleton is challenging, especially with reconstructions necessitating free vascularized bone grafts. The need for further combined orthodontic-orthognathic intervention at skeletal maturity must be anticipated. The growth potential of these grafts and potential new problems associated with performing a sagittal split osteotomy at skeletal maturity are poorly understood. METHODS: A retrospective chart review revealed 11 patients who underwent reconstruction with a free fibula at The Hospital for Sick Children from 1990 to 2000. Radiographic and photographic studies were assessed for long-term growth of the reconstructed mandible, with follow-up ranging from 2 to 12 years. RESULTS: Of the 11 patients who underwent reconstruction with a free fibula, two had surgery at skeletal maturity, two moved out of the country, one died as a result of her malignancy, and one was lost to follow-up. The remaining five patients are being followed by the craniofacial and orthodontic services and have not reached skeletal maturity. Of the two patients who have had orthognathic surgery, the one patient whose reconstruction involved the temporomandibular joint exhibited no growth on the reconstructed side and required a 57-mm advancement on the reconstructed side. The other patient, who had preservation of the temporomandibular joint at the time of reconstruction, required only a 5-mm advancement on the reconstructed side. Both patients had significant surgical complications as a result of the initial reconstructive techniques. Technical modifications necessary at the initial reconstruction became apparent when the authors performed a sagittal split osteotomy on the reconstructed side. CONCLUSIONS: Certain technical modifications to the original free fibula reconstructed pediatric mandible should be considered in anticipation of the need for a subsequent bilateral sagittal split at skeletal maturity.

Adolescent↗