Serum aluminium concentration and aluminium deposits in bone in patients receiving haemodialysis.

Serum aluminium concentrations and biopsy specimens of bone were examined in 56 patients with end stage chronic renal failure receiving maintenance haemodialysis. Deposits of aluminium in bone specimens were often associated with low bone formation with or without osteomalacia. Serum aluminium concentrations of greater than 3.7 mumol/l (10 micrograms/100 ml) indicated a high probability of deposits of aluminium in bone specimens, although high serum concentrations did not predict the type of renal bone disease. Biopsy of the bone is the best method of detecting aluminium intoxication of bone. A serum aluminium concentration of 3.7 mumol/l should be the threshold beyond which bone biopsy should be performed to confirm an overload of aluminium and identify histological bone changes induced by aluminium.     

Material matters: a mechanostat-based perspective on bone development in osteogenesis imperfecta and hypophosphatemic rickets

This perspective paper presents a hypothesis that links abnormalities of bone material with densitometric findings in two congenital metabolic bone disorders, osteogenesis imperfecta type I (OI) and X-linked hypophosphatemic rickets (XLH). Analyses of iliac bone samples from OI patients have shown that material bone density is elevated and that the bone material is abnormally stiff in this disorder. Therefore, a given mechanical load on an OI bone will generate a smaller than normal deformation. This in turn should lead osteocytes, the putative mechanosensing cells, to systematically underestimate the prevailing mechanical forces. According to the mechanostat model, bone strength should then be adapted to the underestimated mechanical loads, which means that bone architecture and mass remain below requirements. Available densitometric studies are in accordance with this hypothesis. In XLH, a mild mineralization defect persists despite treatment. This mineralization defect should lead to soft bone material. In analogy to the above model for OI, mechanical loads should be overestimated, resulting in increased densitometric parameters of bone strength. Indeed, lumbar spine areal bone mineral density is usually elevated in such patients.     

Biodegradable bone regeneration synthetic scaffolds: in tissue engineering

A growing array of synthetic bone regeneration scaffolds has been used or investigated over the last century. These scaffolds aim to provide a three dimensional substrate for bone cells to populate on and function appropriately. To serve this function, these scaffolds should be biocompatible and biodegradable at a rate commensurate with bone remodelling. Their mechanical properties should also be similar to those of the bone regeneration site. In this review, the main families of synthetic bone scaffolds were taxonomised and expounded. The main focus of this paper will be on the basic sciences principles and properties of clinical available as well as experimental synthetic bone scaffolds. Special emphasis was put on scaffolds developed over the last ten years.     

Stability of RNA isolated from human trabecular bone at post-mortem and surgery

To determine the reliability of gene expression studies in human post-mortem bone, it is important to evaluate the stability of RNA isolated from such tissues as a function of the post-mortem interval. The stability of total RNA and bone-specific mRNA species was examined in bone samples obtained from routine autopsies and at surgery. The optimal temperature for any storage and transport of the bone before RNA isolation was shown to be 4 degrees C, and RT-PCR analysis is the preferred technique for the analysis of gene expression in post-mortem bone as it tolerates partial RNA degradation. For gene expression studies in bone, post-mortem cases, with a post-mortem interval of less than 48 h, should be selected, and the time that bone is stored after retrieval at autopsy or surgery should be kept to a minimum. Overall, our findings indicate that with appropriate storage and handling, RNA can be reliably isolated from human bone obtained at post-mortem and surgery to study ex vivo the pattern of gene expression in healthy individuals and in patients with musculoskeletal diseases such as osteoporosis and osteoarthritis.     

Bone formation by revascularized periosteal and bone grafts, compared with traditional bone grafts.

Three groups of dogs were studied to compare the bone formation obtained with traditional bone grafting techniques, and that obtained with revascularized periosteum or revascularized bone grafts--all in unstressed bone. Revascularized periosteum did not produce a significant amount of bone in this unstressed model. At 4 months the revascularized rib grafts had a slightly greater tolerance to stress at the callus site than traditional bone grafts, but the incidence of non-union was the same. We conclude that the use of revascularized bone grafts should be reserved for situations in which traditional bone grafting techniques are unlikely to be successful.     

Glucocorticoid-induced osteoporosis

Osteoporosis is a common and serious complication of glucocorticoid therapy, resulting in increased risk of fragility fractures. Recent studies indicate that fracture risk is increased even at low doses of glucocorticoids and that this increased risk is seen soon after the commencement of glucocorticoid therapy. Both increased bone resorption and reduced bone formation contribute to bone loss, which affects cortical and cancellous sites. A number of interventions have been shown to prevent glucocorticoid-induced bone loss, although the strongest evidence exists for the bisphosphonates etidronate, alendronate and risedronate. Primary prevention of bone loss should be considered in all high-risk individuals taking oral glucocorticoids for 3 months or more, for example those aged 65 years or over or those with a previous fragility fracture. In other glucocorticoid-treated individuals, the decision to treat should be based on bone densitometry.     

The role of primary bone grafting in complex craniomaxillofacial trauma

The role of craniofacial surgical techniques and immediate bone grafting in the management of complex craniofacial trauma has been reviewed. Four hundred and one patients with complex facial injuries have been treated. Two hundred and forty-one primary bone and cartilage grafts have been performed in 66 patients. Complex facial injuries should be managed by direct exposure, reduction, and fixation of all fractures utilizing interfragmentary wiring. Very comminuted or absent bone is replaced by immediate bone grafting, producing a stable skeleton without the need for external fixation devices. Associated mandibular fractures are managed with rigid internal fixation utilizing A-O technique. Results of immediate bone grafting have been excellent, and complications are rare. All deformities should be corrected, whenever possible, during the initial operation. This one-stage reconstruction of even the most complex facial injuries will prevent severe postoperative traumatic deformity and disability that may be extremely difficult or impossible to correct secondarily.     

Body size, body shape, and long bone strength in modern humans

To identify behaviorally significant differences in bone structure it is first necessary to control for the effects of body size and body shape. Here the scaling of cross-sectional geometric properties of long bone diaphyses with different "size" measures (bone length, body mass, and the product of bone length and body mass) are compared in two modern human populations with very different body proportions: Pecos Pueblo Amerindians and East Africans. All five major long bones (excluding the fibula) were examined. Mechanical predictions are that cortical area (axial strength) should scale with body mass, while section modulus (bending/torsional strength) should scale with the product of body mass and moment arm length. These predictions are borne out for section moduli, when moment arm length is taken to be proportional to bone length, except in the proximal femoral diaphysis, where moment arm length is proportional to mediolateral body breadth (as would be expected given the predominance of M-L bending loads in this region). Mechanical scaling of long bone bending/torsional strength is similar in the upper and lower limbs despite the fact that the upper limb is not weight-bearing. Results for cortical area are more variable, possibly due to a less direct dependence on mechanical factors. Use of unadjusted bone length alone as a "size" measure produces misleading results when body shape varies significantly, as is the case between many modern and fossil hominid samples. In such cases a correction factor for body shape should be incorporated into any "size" standardization.     

Demonstration of the Ground Substance of Cartilage, Bone, and Teeth

A slab of bone about 5 mm. thick is decalcified in 5% HCl, washed, and placed for several days to 2-3 weeks in 3% KOH in 20% glycerin (if the bone is medium sized); for small bones the KOH should be decreased to 1%, and for large bones it may be increased to 5%. The solution is changed frequently. When the bone begins to dissociate, it should be removed and washed in water till all traces of alkali are removed. The specimen is passed through 3 changes of dioxane into paraffin, and then through a second paraffin bath into the final paraffin. Sections are cut at 10-12 μ and stained with VanGieson's picro-fuchsin or with orcein.     

A combined rectus abdominis musculocutaneous flap and vascularized iliac bone graft with double vascular pedicles

Although a free vascularized iliac bone graft has been successfully used for the reconstruction of large bone defects, there is a serious problem of how to repair in one stage patients having a large bone defect with a very wide skin defect. A free combined rectus abdominis musculocutaneous flap and vascularized iliac bone graft with double vascular pedicles seems to be one of the most suitable methods for patients having large defects of both bone and skin. Based on our patient, the main advantage of this flap is the extreme width of the skin territory. The pedicle vessels are large and long, and the donor scar can be made in an unexposed area. This flap should be considered for use in one-stage reconstructions of large defects of both bone and skin in the leg region.     

Treatment of Niemann-Pick disease type B by allogeneic bone marrow transplantation.

Allogenic bone marrow transplantation was carried out on a 3 year old girl with Niemann-Pick disease type B. Successful engraftment was achieved, and nine months after the procedure there was definite clearing of the sphingomyelin from the liver and pronounced clearing from the bone marrow. Any patient with Niemann-Pick disease type B complicated by early or severe hepatic impairment should be considered for bone marrow transplantation.     

"I have a bone stuck in my throat".

Any patient claiming to have swallowed a bone and to have it stuck in his throat should be believed. The bone will probably not show in a lateral radiograph of the neck. The bone must be looked for and removed: otherwise the patient may die of septic complications.     

Management of osteoporosis

Osteoporosis or osteopenia occurs in about 44 million Americans, resulting in 1.5 million fragility fractures per year. The consequences of these fractures include pain, disability, depression, loss of independence, and increased mortality. The burden to the healthcare system, in terms of cost and resources, is tremendous, with an estimated direct annual USA healthcare expenditure of about $17 billion. With longer life expectancy and the aging of the baby-boomer generation, the number of men and women with osteoporosis or low bone density is expected to rise to over 61 million by 2020. Osteoporosis is a silent disease that causes no symptoms until a fracture occurs. Any fragility fracture greatly increases the risk of future fractures. Most patients with osteoporosis are not being diagnosed or treated. Even those with previous fractures, who are at extremely high risk of future fractures, are often not being treated. It is preferable to diagnose osteoporosis by bone density testing of high risk individuals before the first fracture occurs. If osteoporosis or low bone density is identified, evaluation for contributing factors should be considered. Patients on long-term glucocorticoid therapy are at especially high risk for developing osteoporosis, and may sustain fractures at a lower bone density than those not taking glucocorticoids. All patients should be counseled on the importance of regular weight-bearing exercise and adequate daily intake of calcium and vitamin D. Exposure to medications that cause drowsiness or hypotension should be minimized. Non-pharmacologic therapy to reduce the non-skeletal risk factors for fracture should be considered. These include fall prevention through balance training and muscle strengthening, removal of fall hazards at home, and wearing hip protectors if the risk of falling remains high. Pharmacologic therapy can stabilize or increase bone density in most patients, and reduce fracture risk by about 50%. By selecting high risk patients for bone density testing it is possible to diagnose this disease before the first fracture occurs, and initiate appropriate treatment to reduce the risk of future fractures.     

Overview of osteoporosis.

Osteoporosis is a common age-related disorder manifested clinically by skeletal fractures, especially fractures of the vertebrae, hip, and distal forearm. The major cause of these fractures is low bone mass, although an increase in trauma due to falls in the elderly also contributes. There are multiple causes for the low bone mass which, in any given individual, may contribute differently to the development of the osteopenia. The most important groups of causes are failure to achieve adequate peak bone mass, slow bone loss due to processes relating to aging, the menopause in women, and a variety of sporadic behavioral, nutritional, and environmental factors that affect bone mass in some but not in other individuals. The most important approach is prevention. Drugs and behavioral factors known to cause bone loss should be eliminated and perimenopausal women should be evaluated for possible preventive administration of estrogen. For patients with fractures due to established osteoporosis, the only drugs approved by the Food and Drug Administration are the antiresorptive agents calcium, estrogen, and calcitonin. Formation-stimulating regimens, however, are being developed and may be available for clinical use in the foreseeable future. These regimens may be capable of increasing bone mass to above the fracture threshold, thereby resulting in a clinical cure of the osteoporosis.     

Normal bone turnover markers in a patient with active Paget's disease of bone: response to treatment with zoledronic acid

The treatment of Paget's disease of bone (PDB) aims at the suppression of abnormal bone turnover; bisphosphonates are currently the treatment of choice. Indications for antiresorptive treatment in symptomatic patients with PDB include bone or joint pain, neurological complications, surgery planned at an active pagetic site and hypercalcaemia from immobilisation. The goals of antiresorptive treatment are clinical improvement and biochemical remission, as assessed by the normalisation of bone turnover markers. Clinical deterioration, especially bone pain, should be considered before deciding to treat patients with late sclerotic (burned-out) PDB. Bone scintigraphy may be of importance in these patients, because it depicts increased osteoblastic activity, when bone markers may not. We present a case of late sclerotic PDB with clinical deterioration but normal bone turnover markers, who experienced significant clinical improvement after treatment with zoledronic acid.     

Bone densitometry: assessing the effects of growth hormone treatment in adults

Dual-energy X-ray absorptiometry (DXA) is the reference method for the measurement of bone mineral mass at different skeletal sites. It has been widely used in recent years to assess the effects of growth hormone (GH) treatment on bone metabolism. In normal individuals, bone mineral content (BMC) and density (BMD), as assessed using DXA, correlate with body size. Therefore, using DXA in patients with congenital GH deficiency (GHD), who have a smaller body frame, would be expected to result in lower bone mass. Thus, comparisons with reference data derived from populations of normal body size are invalid. The evaluation of the effects of GH administration should take into account the possible effects of GH on bone size, not only in children, but also in adults. The enlargement of bone, due to stimulation of the periosteal apposition, may partially mask an increase in BMC, resulting in little or no change in BMD. The ability of GH to affect bone area therefore requires analysis of the possible changes in bone area and BMC, as well as BMD. This issue has been poorly handled in the studies published to date. Lastly, the acceleration of bone turnover induced by GH leads to an increase in bone remodelling space, which in turn is associated with a reduction in BMC and BMD, independent of the net balance between breakdown and formation in each metabolic unit. This bone loss is completely reversible when the remodelling space returns to previous levels. This phenomenon must be taken into account when analysing the effects of GH treatment on bone mass, because a net gain in bone mass may be found in long-term GH treatment or after GH discontinuation, even if bone loss was evident during the first 6 months of treatment. In conclusion, the interpretation of bone density data in patients with GHD, and after GH administration, should take into account some of the methodological aspects of bone densitometry, as well as the specific actions of GH on bone metabolism and body composition.     

Dental replacement resorption after bone grafting to the alveolar cleft

In a review of 100 consecutively performed bone grafts to the alveolar cleft, replacement resorption was found in 7 teeth adjacent to the cleft. Damage to the periodontal tissues during surgery is considered to be the main cause of this complication: granulation tissue from the bone graft may have some influence. Treatment of the affected teeth eventually includes extraction or surgical removal. To minimize the risk for this complication, we suggest that bone grafting should be done when the canine (or lateral incisor) is in an early stage of eruption and that orthodontic uprighting of the medial incisor should be done after surgery.     

3D strain map of axially loaded mouse tibia: a numerical analysis validated by experimental measurements

A combined experimental/numerical study was performed to calculate the 3D octahedral shear strain map in a mouse tibia loaded axially. This study is motivated by the fact that the bone remodelling analysis, in this in vivo mouse model should be performed at the zone of highest mechanical stimulus to maximise the measured effects. Accordingly, it is proposed that quantification of bone remodelling should be performed at the tibial crest and at the distal diaphysis. The numerical model could also be used to furnish a more subtle analysis as a precise correlation between local strain and local biological response can be obtained with the experimentally validated numerical model.     

Percent osteonal bone versus osteon counts: the variable of choice for estimating age at death.

Ahlqvist and Damsten's (1969) modification of the Kerley (1965) method for histological age estimation uses percent osteonal bone, rather than actual osteon counts, in order to eliminate the difficulty of distinguishing between intact and fragmentary osteons. Since their method has been developed for the femur only, and several more recent methods have been proposed that utilize percent osteonal bone, a study was undertaken to ascertain the relative value of percent osteonal bone compared with osteon counts to estimate age at death for the radius, tibia, and fibula. First the question of how much of the cross-section of a bone should be sampled was addressed by comparing the results of regression against age for percent osteonal bone derived from sampling only four fields with those derived from the entire cross-section of the radius. A significant age association was found only when the entire cross-section was sampled. In order to evaluate the relative merit of using either percent osteonal bone, or osteon counts to estimate age, each variable was regressed against age. Significant correlation coefficients were found for all three bones when the independent variable was osteon counts. When percent osteonal bone was employed, a significant correlation was found only for the radius. Stepwise linear regression found osteon counts for the fibula alone to be the best age predictor. Finally, a repeated measures analysis of variance revealed that percent osteonal bone and osteon counts both differ among the three bones within an individual. Based upon these results, osteon counts, rather than percent osteonal bone, should be the variable of choice when developing histological age predicting methods.     

The split calvarial graft donor site in the elderly: a study in cadavers

In 37 cadavers of average age 75.5 years, the calvarium was studied. In all, the diploe and outer and inner tables were found to be definite layers. Although the parietal bone thickness did decrease with age in this study, there was no correlation between age and the outer table or diploe thickness. No significant change with age occurred in the occipital bone. Although this study supports the use of split calvarial grafts in older patients without the necessity for a craniotomy, the relative brittleness of this bone in this population should be considered.