Trabecular Resorption Research Articles

Collapse-Related Bone Changes in Osteonecrotic Femoral Heads at Multidetector CT: Comparison between Femoral Heads with Limited and Advanced Collapse.

Aim:To assess the frequency of bone changes in resected osteonecrotic femoral head (ONFH) specimens at multidetector computed tomography (MDCT) and compare their frequencies between ONFH with limited or advanced collapse.Method:Fourteen ONFH were imaged using MDCT (n = 14) and microcomputed tomography ([µCT]; n = 8). Preoperative staging was performed using radiographs and MRI. Coronal reformats of MDCT images of the specimens were analyzed using the grid overlay method. There were 2,933 grid boxes containing cortical bone and 10,596 containing trabecular bone. Two MSK radiologists assessed in every grid box the presence of interface-related sclerosis, cortical bone interruption, trabecular bone interruption, and trabecular bone resorption. The frequency of grid boxes with bone changes at MDCT was calculated and compared between ONFH with limited (<1.5 mm) or advanced (≥1.5 mm) collapse.Results:For both readers R1 and R2, there were 1111/10596 (10.5%) and 1362/10596 (12.9%) grid boxes with interface-related bone sclerosis, 557/2933 (19%) and 413/2933 (14.1%) with cortical bone interruption, 796/10596 (7.5%) and 665/10596 (6.3%) with trabecular bone interruption, and 331/10596 (3.1%) and 595/10596 (5.6%) with trabecular bone resorption. The frequency of grid boxes with cortical interruption and trabecular bone resorption was significantly higher in ONFH with advanced than in ONFH with limited collapse. There was no significant difference in frequency of grid boxes with trabecular interruption and interface-related bone sclerosis between ONFH with advanced or limited collapse.Conclusion:Cortical interruption and trabecular resorption, but not trabecular interruption, were more frequent in osteonecrotic femoral heads with advanced than with limited collapse.

A Bisphosphonate With a Low Hydroxyapatite Binding Affinity Prevents Bone Loss in Mice After Ovariectomy and Reverses Rapidly With Treatment Cessation.

ABSTRACTBisphosphonates (BPs) are a mainstay of osteoporosis treatment; however, concerns about bone health based on oversuppression of remodeling remain. Long‐term bone remodeling suppression adversely affects bone material properties with microdamage accumulation and reduced fracture toughness in animals and increases in matrix mineralization and atypical femur fractures in patients. Although a “drug holiday” from BPs to restore remodeling and improve bone quality seems reasonable, clinical BPs have long functional half‐lives because of their high hydroxyapatite (HAP) binding affinities. This places a practical limit on the reversibility and effectiveness of a drug holiday. BPs with low HAP affinity and strong osteoclast inhibition potentially offer an alternative approach; their antiresorptive effect should reverse rapidly when dosing is discontinued. This study tested this concept using NE‐58025, a BP with low HAP affinity and moderate osteoclast inhibition potential. Young adult female C57Bl/6 mice were ovariectomized (OVX) and treated with NE‐58025, risedronate, or PBS vehicle for 3 months to test effectiveness in preventing long‐term bone loss. Bone microarchitecture, histomorphometry, and whole‐bone mechanical properties were assessed. To test reversibility, OVX mice were similarly treated for 3 months, treatment was stopped, and bone was assessed up to 3 months post‐treatment. NE‐58025 and RIS inhibited long‐term OVX‐induced bone loss, but NE‐58025 antiresorptive effects were more pronounced. Withdrawing NE‐58025 treatment led to the rapid onset of trabecular resorption with a 200% increase in osteoclast surface and bone loss within 1 month. Cessation of risedronate treatment did not lead to increases in resorption indices or bone loss. These results show that NE‐58025 prevents OVX‐induced bone loss, and its effects reverse quickly following cessation treatment in vivo. Low‐HAP affinity BPs may have use as reversible, antiresorptive agents with a rapid on/off profile, which may be useful for maintaining bone health with long‐term BP treatment. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Early Changes in Cement-Bone Fixation Using a Novel Rat Knee Replacement Model.

Trabecular resorption from interdigitated regions between cement and bone has been found in postmortem-retrieved knee replacements, but the viability of interdigitated bone, and the mechanism responsible for this bone loss is not known. In this work, a Sprague-Dawley (age 12 weeks) rat knee replacement model with an interdigitated cement-bone interface was developed. Morphological and cellular changes in the interdigitated region of the knee replacement over time (0, 2, 6, or 12 weeks) were determined for ovariectomy (OVX) and Sham OVX treatment groups. Interdigitated bone volume fraction (BV/TV) increased with time for Sham OVX (0.022 BV/TV/wk) and OVX (0.015 BV/TV/wk) group, but the rate of increase was greater for the Sham OVX group (p = 0.0064). Tissue mineral density followed a similar increase with time in the interdigitated regions. Trabecular resorption, when it did occur, started at the cement border with medullary-adjacent bone in the presence of osteoclasts. There was substantial loss of viable bone (~80% empty osteocyte lacunae) in the interdigitated regions. Pre-surgical fluorochrome labels remained in the interdigitated regions, and did not diminish with time, indicating that the bone was not remodeling. There was also some evidence of continued surface mineralization in the interdigitated region after cementing of the knee, but this diminished over time. Statement of clinical significance: Interdigitated bone with cement provides mechanical stability for success of knee replacements. Improved understanding of the fate of the interdigitated bone over time could lead to a better understanding of the loosening process and interventions to prevent loss of fixation. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:2163-2171, 2019.

Effect of esculetin on bone metabolism in ovariectomized rats

OBJECTIVETo determine the effect of an esculetin formulation (at 97.4% purity) on osteoporosis, and to investigate the potential underlying molecular mechanism(s). METHODSSixty specific pathogen free-grade female Wistar rats were randomly assigned to three groups: blank control (n = 12), sham (n = 12), and model (n = 36). The model group were bilaterally ovariectomized. The sham group had the tissue surrounding the ovaries removed, while the ovaries were retained. After 3 months, the model group was randomly divided into three subgroups: OVX (n = 12), positive control (n = 12), and esculetin (n = 12). The positive control group and the esculetin group were intragastrically administered diethylstilbestrol (0.046 mg • kg−1 • d−1) or esculetin (384 mg • kg−1 • d−1), respectively, once per day for 6 consecutive days; medication administration was then stopped for 1 d, before being administered for another 6 consecutive days. All rats were treated for 3 months. Samples were collected at the end of the treatment period. An Osteocore3 Digital 2D bone densitometer was used to test the bone mineral density, and histomorphometric analysis was performed to measure bone mass, bone formation, and bone resorption. Enzyme-linked immunosorbent assay analysis was used to measure the serum concentrations of interleukin-6 (IL-6), osteoprotegerin (OPG), and receptor activator of nuclear factor-kappa B ligand (RANKL). Immunohistochemistry and in situ hybridization were performed to detect the protein and mRNA expressions of OPG and RANKL in osteoblasts and bone marrow stromal cells. RESULTSCompared with the OVX group, the esculetin group had significantly greater femoral bone mineral density and tibial trabecular bone volume, and significantly smaller trabecular resorption surface. The percentage of trabecular formation surface, average osteoid width, trabecular bone mineralization rate, and cortical bone mineralization rate did not significantly differ between groups. Compared with the sham group, the esculetin group had significantly decreased serum levels of IL-6 and RANKL, and significant downregulation of RANKL protein and mRNA expression levels in osteoblasts and bone marrow stromal cells; however, there was no significant difference between groups in OPG. CONCLUSIONEsculetin can increase bone mass by upregulating RANKL expression in osteoblasts and bone marrow stromal cells, and decreasing serum IL-6 concentration. This indicates that the therapeutic effect of esculetin on osteoporosis occurs via decreased bone resorption.

Longitudinal Effects of Single Hindlimb Radiation Therapy on Bone Strength and Morphology at Local and Contralateral Sites.

Radiation therapy (RTx) is associated with increased risk for late-onset fragility fractures in bone tissue underlying the radiation field. Bone tissue outside the RTx field is often selected as a "normal" comparator tissue in clinical assessment of fragility fracture risk, but the robustness of this comparison is limited by an incomplete understanding of the systemic effects of local radiotherapy. In this study, a mouse model of limited field irradiation was used to quantify longitudinal changes in local (irradiated) and systemic (non-irradiated) femurs with respect to bone density, morphology, and strength. BALB/cJ mice aged 12 weeks underwent unilateral hindlimb irradiation (4 × 5 Gy) or a sham procedure. Femurs were collected at endpoints of 4 days before treatment and at 0, 1, 2, 4, 8, 12, and 26 weeks post-treatment. Irradiated (RTx), Contralateral (non-RTx), and Sham (non-RTx) femurs were imaged by micro-computed tomography and mechanically tested in three-point bending. In both the RTx and Contralateral non-RTx groups, the longer-term (12- to 26-week) outcomes included trabecular resorption, loss of diaphyseal cortical bone, and decreased bending strength. Contralateral femurs generally followed an intermediate response compared with RTx femurs. Change also varied by anatomic compartment; post-RTx loss of trabecular bone was more profound in the metaphyseal than the epiphyseal compartment, and cortical bone thickness decreased at the mid-diaphysis but increased at the metaphysis. These data demonstrate that changes in bone quantity, density, and architecture occur both locally and systemically after limited field irradiation and vary by anatomic compartment. Furthermore, the severity and persistence of systemic bone damage after limited field irradiation suggest selection of control tissues for assessment of fracture risk or changes in bone density after radiotherapy may be challenging. © 2017 American Society for Bone and Mineral Research.

Trabecular resorption patterns of cement–bone interlock regions in total knee replacements

Aseptic loosening of joint replacements remains an important clinical problem. This work explores the process and pattern of trabecular bone resorption responsible for loss of interface fixation. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:2773-2780, 2017.

Peri-Implant Distribution of Polyethylene Debris in Postmortem-Retrieved Knee Arthroplasties: Can Polyethylene Debris Explain Loss of Cement-Bone Interlock in Successful Total Knee Arthroplasties?

BackgroundLoss of mechanical interlock between cement and bone with in vivo service has been recently quantified for functioning, nonrevised, cemented total knee arthroplasties (TKAs). The cause of interlocking trabecular resorption is not known. The goal of this study is to quantify the distribution of PE debris at the cement-bone interface and determine if polyethylene (PE) debris is locally associated with loss of interlock. MethodsFresh, nonrevised, postmortem-retrieved TKAs (n = 8) were obtained en bloc. Laboratory-prepared constructs (n = 2) served as negative controls. The intact cement-bone interface of each proximal tibia was embedded in Spurr’s resin, sectioned, and imaged under polarized light to identify birefringent PE particles. PE wear particle number density was quantified at the cement-bone interface and distal to the interface, and then compared with local loss of cement-bone interlock. ResultsThe average PE particle number density for postmortem-retrieved TKAs ranged from 8.6 (1.3) to 24.9 (3.1) particles/mm2 (standard error) but was weakly correlated with years in service. The average particle number density was twice as high as distal (>5mm) to the interface compared to at the interface. The local loss of interlock at the interface was not related to the presence, absence, or particle density of PE. ConclusionPE debris can migrate extensively along the cement-bone interface of well-fixed tibial components. However, the amount of local bone loss at the cement-bone interface was not correlated with the amount of PE debris at the interface, suggesting that the observed loss of trabecular interlock in these well-fixed TKAs may be due to alternative factors.

Changes in microgaps, micromotion, and trabecular strain from interlocked cement‐trabecular bone interfaces in total knee replacements with in vivo service

The initial fixation of cemented Total Knee Replacements (TKRs) relies on mechanical interlock between cement and bone, but loss of interlock occurs with in vivo service. In this study, cement-trabeculae gap morphology and micromechanics were measured for lab prepared (representing post-operative state) and postmortem retrieval (with in vivo remodeling) TKRs to determine how changes in fixation affect local micromechanics. Small specimens taken from beneath the tibial tray were loaded with 1 MPa axial compression and the local micromechanics of the trabeculae-cement interface was quantified using digital image correlation. Lab prepared trabeculae that initially interlock with cement had small gaps (ave:14 μm) and limited micromotion (ave:1 μm) which were larger near the cement border. Trabecular resorption was prevalent following in vivo service; interface gaps became larger (ave:40 μm) and micromotion increased (ave:6 μm), particularly near the cement border. Interlocked trabeculae from lab prepared specimens exhibited strains that were 20% of the supporting bone strain, indicating the trabeculae were initially strain shielded. The spatial and temporal progression of gaps, micromotion, and bone strain was complex and much more variable for post-mortem retrievals compared to the lab prepared specimens. From a clinical perspective, attaining more initial interlock results in cement-bone interfaces that are better fixed with less micromotion. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1019-1025, 2016.

Ergonomic task reduction prevents bone osteopenia in a rat model of upper extremity overuse.

We evaluated the effectiveness of ergonomic workload reduction of switching rats from a high repetition high force (HRHF) lever pulling task to a reduced force and reach rate task for preventing task-induced osteopenic changes in distal forelimb bones. Distal radius and ulna trabecular structure was examined in young adult rats performing one of three handle-pulling tasks for 12 wk: 1) HRHF, 2) low repetition low force (LRLF); or 3) HRHF for 4 wk and than LRLF thereafter (HRHF-to-LRLF). Results were compared to age-matched controls rats. Distal forelimb bones of 12-wk HRHF rats showed increased trabecular resorption and decreased volume, as control rats. HRHF-to-LRLF rats had similar trabecular bone quality as control rats; and decreased bone resorption (decreased trabecular bone volume and serum CTX1), increased bone formation (increased mineral apposition, bone formation rate, and serum osteocalcin), and decreased osteoclasts and inflammatory cytokines, than HRHF rats. Thus, an ergonomic intervention of HRHF-to-LRLF prevented loss of trabecular bone volume occurring with prolonged performance of a repetitive upper extremity task. These findings support the idea of reduced workload as an effective approach to management of work-related musculoskeletal disorders, and begin to define reach rate and load level boundaries for such interventions.

Long-term loss of osteoclasts and unopposed cortical mineral apposition following limited field irradiation.

Late-onset fragility fractures are a common complication following radiotherapy for metastatic disease and soft tissue sarcomas. Using a murine hindlimb focal irradiation model (RTx), we quantified time-dependent changes in osteoclasts and mineral apposition rate (MAR). Mice received either a single, unilateral 5 Gy exposure or four fractionated doses (4 × 5 Gy). Osteoclast numbers and MAR were evaluated histologically at 1, 2, 4, 8, 12, and 26 weeks post-RTx. Radiation induced an early, transient increase in osteoclasts followed by long-term depletion. Increased osteoclast numbers correlated temporally with trabecular resorption; the resorbed trabeculae were not later restored. Radiotherapy did not attenuate MAR at any time point. A transient, early increase in MAR was noted in both RTx groups, however, the 4 × 5 Gy group exhibited an unexpected spike in MAR eight weeks. Persistent depletion of osteoclasts permitted anabolic activity to continue unopposed, resulting in cortical thickening. These biological responses likely contribute to post-radiotherapy bone fragility via microdamage accumulation and matrix embrittlement in the absence of osteoclastic remodeling, and trabecular resorption-induced decrease in bone strength. The temporal distribution of osteoclast numbers suggests that anti-resorptive therapies may be of clinical benefit only if started prior to radiotherapy and continued through the following period of increased osteoclastic remodeling.

Osteoclast inhibition impairs chondrosarcoma growth and bone destruction.

Because Chondrosarcoma is resistant to available chemotherapy and radiation regimens, wide resection is the mainstay in treatment, which frequently results in high morbidity and which may not prevent local recurrence. There is a clear need for improved adjuvant treatment of this malignancy. We have observed the presence of osteoclasts in the microenvironment of chondrosarcoma in human pathological specimens. We utilized the Swarm rat chondrosarcoma (SRC) model to test the hypothesis that osteoclasts affect chondrosarcoma pathogenesis. We implanted SRC tumors in tibia of Sprague-Dawley rats and analyzed bone histologically and radiographically for bone destruction and tumor growth. At three weeks, tumors invaded local bone causing cortical disruption and trabecular resorption. Bone destruction was accompanied by increased osteoclast number and resorbed bone surface. Treatment of rats with the zoledronic acid prevented cortical destruction, inhibited trabecular resorption, and resulted in decreased tumor volume in bone. To confirm that inhibition of osteoclasts per se, and not off-target effects of drug, was responsible for the prevention of tumor growth and bone destruction, we implanted SRC into osteopetrotic rat tibia. SRC-induced bone destruction and tumor growth were impaired in osteopetrotic bone compared with control bone. The results from our animal model demonstrate that osteoclasts contribute to chondrosarcoma-mediated bone destruction and tumor growth and may represent a therapeutic target in particular chondrosarcoma patients.

Increased initial cement–bone interlock correlates with reduced total knee arthroplasty micro-motion following in vivo service

Aseptic loosening of cemented tibial components in total knee arthroplasty (TKA) has been related to inadequate cement penetration into the trabecular bone bed during implantation. Recent postmortem retrieval work has also shown there is loss of interlock between cement and bone by resorption of trabeculae at the interface. The goal of this study was to determine if TKAs with more initial interlock between cement and bone would maintain more interlock with in vivo service (in the face of resorbing trabeculae) and have less micro-motion at the cement–bone interface. The initial (created at surgery) and current (after in vivo service) cement–bone interlock morphologies of sagittal implant sections from postmortem retrieved tibial tray constructs were measured. The implant sections were then functionally loaded in compression and the micro-motion across the cement–bone interface was quantified. Implant sections with less initial interdigitation between cement and bone and more time in service had less current cement–bone interdigitation (r2=0.86, p=0.0002). Implant sections with greater initial interdigitation also had less micro-motion after in vivo service (r2=0.36, p=0.0062). This work provides direct evidence that greater initial interlock between cement and bone in tibial components of TKA results in more stable constructs with less micro-motion with in vivo service.

Loss of Cement-bone Interlock in Retrieved Tibial Components from Total Knee Arthroplasties

Aseptic loosening continues to be a short- and long-term complication for patients with cemented TKAs. Most studies to this point have evaluated tibial component fixation via radiographic changes at the implant-bone interface and quantification of component migration; direct assessment of morphologic features of the interface from functioning TKAs may provide new information regarding how TKAs function and are fixed to bone. In a postmortem retrieval study, we asked: (1) What are the morphologic features at the cement-trabecular bone interface in retrieved tibial components? (2) Do constructs with greater time in service have less cement-trabecular bone interlock? (3) Do constructs with more estimated initial interlock sustain more interlock with in vivo service? Fourteen postmortem retrieved tibial components with time in service from 0 to 20 years were sectioned and imaged at high resolution, and the current contact fraction, estimated initial interdigitation depth, current interdigitation depth, and loss of interdigitation depth were quantified at the cement-bone interface. Estimated initial interdigitation depth was calculated from the initial mold shape of the cement mantle that forms around the individual trabeculae at the time of surgery. Loss of interdigitation depth was the difference between the initial and current interdigitation depth. There was resorption of trabeculae that initially interlocked with the cement in the postmortem retrievals as evidenced by the differences between current interdigitation and the estimated original interdigitation. The current contact fraction (r(2) = 0.54; p = 0.0027) and current interdigitation depth (r(2) = 0.33; p = 0.033) were less for constructs with longer time in service. The current contact fraction for implants with 10 or more years in service (6.2%; 95% CI, 4.7%-7.7%) was much less than implants with less than 10 years in service (22.9%; 95% CI, 8.9%-37%). Similarly, the current interdigitation depth for implants with 10 or more years in service (0.4 mm; 95% CI, 0.27-0.53 mm) was much less than implants with less than 10 years in service (1.13 mm; 95% CI, 0.48-1.78 mm). The loss of interdigitation depth had a strong positive relationship with time in service (r(2) = 0.74; p < 0.001). Using a two-parameter regression model, constructs with more initial interdigitation depth had greater current interdigitation depth (p = 0.011), but constructs with more time in service also had less current interdigitation depth (p = 0.008). The cement-trabecular bone interlock obtained initially appears to diminish with time with in vivo service by resorption of the trabeculae in the cement interlock region. Our study supports the surgical concept of obtaining sufficient initial cement interlock (approximately 3 mm), with the acknowledgment that there will be loss of interlock with time with in vivo service.

Fluid–structure interactions in micro-interlocked regions of the cement–bone interface

Experimental tests and computational modelling were used to explore the fluid dynamics at the trabeculae–cement interlock regions found in the tibial component of total knee replacements. A cement–bone construct of the proximal tibia was created to simulate the immediate post-operative condition. Gap distributions along nine trabeculae–cement regions ranged from 0 to 50.4 μm (mean = 12 μm). Micro-motions ranged from 0.56 to 4.7 μm with a 1 MPa compressive load to the cement. Fluid–structure analysis between the trabeculae and the cement used idealised models with parametric evaluation of loading direction, gap closing fraction (GCF), gap thickness, loading frequency and fluid viscosity. The highest fluid shear stresses (926 Pa) along the trabecular surface were found for conditions with very thin and large GCFs, much larger than reported physiological levels (∼1–5 Pa). A second fluid–structure model was created with a provision for bone resorption using a constitutive model with resorption velocity proportional to fluid shear rate. A lower cut-off was used, below which bone resorption would not occur (50 s− 1). Results showed that there was initially high shear rates (>1000 s− 1) that diminished after initial trabecular resorption. Resorption continued in high shear rate regions, resulting in a final shape with bone left deep in the cement layer, and is consistent with morphology found in post-mortem retrievals. Small gaps between the trabecular surface and the cement in the immediate post-operative state produce fluid flow conditions that appear to be supra-physiologic; these may cause fluid-induced lysis of trabeculae in the micro-interlock regions.

A new approach to quantify trabecular resorption adjacent to cemented knee arthroplasty

A new micro-computed tomography (μCT) image processing approach to estimate the loss of cement–bone interlock was developed using the concept that PMMA cement flows and cures around trabeculae during the total knee arthroplasty procedure. The initial mold shape of PMMA cement was used to estimate the amount of interdigitated bone at the time of implantation and following in vivo service using enbloc human postmortem retrievals. Laboratory prepared specimens, where there would be no biological bone resorption, were used as controls to validate the approach and estimate errors. The image processing technique consisted of identifying bone and cement from the μCT scan set, dilation of the cement to identify the cement cavity space, and Boolean operations to identify the different components of the interdigitated cement–bone regions. For laboratory prepared specimens, there were small errors in the estimated resorbed bone volume fraction (reBVfr=0.11±0.09) and loss in contact area fraction (CAfr=0.06±0.15). These values would be zero if there were no error in the method. For the postmortem specimens, the resorbed volume fraction (reBVfr=0.85±0.16) was large, meaning that only 15% of the cement mold shape was still filled with bone. The loss of contact area fraction (CAfr=0.84±0.17) was similarly large. This new approach provides a convenient method to visualize and quantify trabecular bone loss from interdigitated regions from postmortem retrievals. The technique also illustrates for the first time that there are dramatic changes in how bone is fixed to cement following in vivo service.

Arm pain after syncope: Diagnosis

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Carbamazepine and bone mineral metabolism.

The status of bone mineral metabolism was studied in 21 epileptic out-patients receiving carbamazepine as the sole anticonvulsant drug. Hypocalcaemia was found in 3, hypophosphataemia in one and elevated serum alkaline phosphatase in 4 of the cases. Serum 25-hydroxyvitamin D values were significantly lower in the patients than in the controls. No statistically significant difference was observed in bone mineral density between the patients and controls. Histomorphometric analysis of the iliac crest cancellous bone did not reveal any statistically significant difference in the amount of trabecular bone or osteoid between the patients and controls, but the patients had an increased amount of trabecular resorption surfaces. An increased amount of osteoid, suggesting histological osteomalacia, was found in 2 of the 18 biopsies. We conclude that epileptic out-patients receiving carbamazepine therapy have vitamin D deficiency and may develop osteomalacic changes in their skeleton.

Trabecular bone dynamics in mice subjected to unilateral sciatic neurectomy assessed by in vivo μCT using monochromatic synchrotron radiation

Monochromatic synchrotron radiation μCT (SRCT) allows quantitative imaging of bone microstructure with high spatial resolutions. Using an SRCT system developed at Japan large‐scale synchrotron radiation facility (Spring‐8), we evaluated the structural changes of tibial metaphyseal trabecular network in ICR mice (n=6) subjected to unloading in one hindlimb induced by sciatic neurectomy at 13 weeks of age. Both hindlimbs were scanned for five minutes at 10 days and 20 days after surgery. The three‐dimensional image was reconstructed with a two‐dimensional filtered backward projection algorithm based on radiographic images acquired with 25‐keV X‐ray over an angular range of 0°–180° with 0.2° steps, providing contiguous images comprised of 1000 × 1000 cubic voxels of 11.7 μm in size. Two reconstructed images at the two different time points were matched by a registration method based on maximizing mutual information. After bone segmentation by setting a threshold value to the hydroxyapatite density of 0.82 g/cm3, local trabecular resorption and formation were quantitated and compared between intact (INT) and sciatic‐neurectomized (SN) hindlimbs. Mechanical unloading reduces the rate of trabecular bone formation but has no effect on the rate of bone resorption as shown in the figure. In both hindlimbs, the number densities of segments and nodes in the trabecular network decreased whereas the trabecular bone thickeness increased, possibly in compensation for the regression of trabecular network. However, the increase of trabecular thickness decreased by 13% in SN hindlimbs.

Biochemical and imaging alterations of renal bone disease in newly detected predialysis and on maintenance dialysis patients

Skeletal involvement in chronic kidney disease manifests long before the initiation of dialysis. This study aimed at identifying the extent of renal bone disease among predialysis and on maintenance dialysis patients. Thirty-two patients (Group 1) on maintenance hemodialysis (MHD) for a variable period of time were compared with 20 newly detected irregularly treated advanced renal failure (immediately predialysis), patients (Group 2) for their clinical, biochemical and imaging features. The mean age of Group 1 and Group 2 patients was 45+/-14 vs. 34+/-15 years (p<0.05). Comparison of blood biochemistries between Groups 1 and 2 showed serum creatinine 9.9+/-2.9 vs. 13.4+/-4.4 mg/dL (p<0.01); calcium 10.1+/-1.8 vs. 7.8+/-1.2 mg/dL (p<0.001); phosphate 4.4+/-1.2 vs. 7.9+/-2.1 mg/dL (p<0.001); alkaline phosphatase 116.4+/-31.7 vs. 85.7+/-30.6 IU/L (p<0.05); and parathormone 71.7+/-48.2 vs. 146.9+/-92.1 pg/mL (p<0.05). Radiological changes present in the 2 groups were as follows: osteopenia 63% vs. 65% (ns); trabecular resorption 53% vs. 20% (p<0.05); soft tissue calcification 31% vs. 10% (p<0.05); bone cysts 16% vs. 26% (ns); and subperiosteal bone resorption 16% vs. 20% (ns). Technetium 99 methylene diphosphonate (Tc-99 MDP) bone scans in both groups of patients showed similar increased uptake in wrist joint, tibia-fibula, costochondral junction, vertebral column, sternum, radius-ulna and mandible. X-ray findings were positive for bone involvement in 59% of cases, and Tc-99 scan was positive in 80% (p<0.05). It is concluded that newly detected, irregularly treated patients with advanced renal failure who are predialysis may present with deranged calcium homeostasis and a high prevalence of bone involvement similar to MHD patients.

Bone and calcium metabolism in subclinical autoimmune hyperthyroidism and hypothyroidism.

Bone turnover is reported to increase in favour of resorption in overt hyperthyroidism and the rate of resorption is associated with the levels of thyroid hormones. Hypothyroidism, on the other hand, was shown to cause no disturbance of calcium kinetics and found to associate lower trabecular resorption surfaces and increased bone cortical thickness. Similar studies are very rare in subclinical thyroid disorders and consequently we aimed to examine calcium and bone metabolism in subclinical thyroid disorders. Thirteen patients with subclinical hyperthyroidism secondary to untreated Graves' disease, 20 patients with subclinical hypothyroidism and 10 healthy subjects participated in this survey. Briefly calcium, phosphorus, and creatinine (Cre), urinary deoxypyridinoline (U-DPD) and serum osteocalcin (OC) were measured as biochemical markers for calcium metabolism. Concerning serum Ca and phosphorus levels, there were no differences between three of the groups, but urinary Ca excretion was higher in subclinical hyperthyroid patients compared to control and hypothyroid subjects. Hypothyroid patients had similar U-DPD levels with control subjects (p = 0.218). Serum OC and U-DPD were higher in subclinical hyperthyroid compared to control subjects (p<0.001 and p<0.001 respectively). We demonstrated a higher bone turnover and greater calcium excretion in subclinical hyperthyroid patients. Additionally, we found that subclinical hypothyroidism is not associated with disturbed calcium metabolism. As persistent increase in bone turnover is responsible for accelerated bone loss, patients with Graves' disease may have increased risk for osteoporosis.