Histochemical assessment on osteoclasts in long bones of toll-like receptor 2 (TLR2) deficient mice.

OBJECTIVE: Toll-like receptor 2 (TLR2), recognizes a wide variety of pathogen-associated molecular patterns such as lipopolysaccharides, peptidoglycans, and lipopeptides, and is generally believed to be present in monocytes, macrophages, dendritic cells, and vascular endothelial cells. However, no histological examination of osteoclasts, which differentiate from precursors common to macrophages/monocytes, has been performed in a non-infected state of TLR2 deficiency. The objective of this study was to examine the histological properties and function of osteoclasts in the long bones of 8-week-old male TLR2 deficient (TLR2-/-) mice to gain insight into TLR2 function in biological circumstances without microbial infection. METHODS: Eight-week-old male wild-type and TLR2-/- mice were fixed with paraformaldehyde solution, and their tibiae and femora were used for micro-CT analysis, immunohistochemistry, transmission electron microscopy, and real-time PCR analysis. RESULTS: TLR2-/- tibiae and femora exhibited increased bone volume of metaphyseal trabeculae and elevated numbers of TRAP-positive osteoclasts. However, the number of multinucleated TRAP-positive osteoclasts was reduced, whereas mononuclear TRAP-positive cells increased, despite the high expression levels of Dc-Stamp and Oc-Stamp. Although TRAP-positive multinucleated and mononuclear osteoclasts showed the immunoreactivity and elevated expression of RANK and siglec-15, they revealed weak cathepsin K-positivity and less incorporation of the mineralized bone matrix, and often missing ruffled borders. It seemed likely that, despite the increased numbers, TLR2-/- osteoclasts reduced cell fusion and bone resorption activity. CONCLUSION: It seems likely that even without bacterial infection, TLR2 might participate in cell fusion and subsequent bone resorption of osteoclasts.

Development and characterization of supramolecular calcitonin assembly and assessment of its interactions with the bone remodelling process.

Osteoporosis is the most common metabolic bone disease, which poses an immense socio-economic burden on the society. Human calcitonin, though safe, is not considered as a therapeutic option because of its high tendency to self-associate to form amyloid fibrils thereby affecting its potency. To circumvent this issue we harnessed the inherent capacity of aggregation and developed an assemblage of human calcitonin monomers, [Supramolecular Calcitonin Assembly (SCAI)], which releases biologically active calcitonin monomers in a sustained manner for a period of at least three weeks. AFM and FT-IR analysis showed that SCA-I is amorphous aggregates of calcitonin monomers. Both SCA-I and monomer released from it demonstrated superior anti-osteoclast activity and proteolytic stability in-vitro. SCA-I upon single injection significantly improved bone formation markers and reduced bone resorption markers in ovariectomized (OVX) rat model of postmenopausal osteoporosis. Micro-CT analysis revealed that calcitonin released from SCA-I exhibits its beneficial effect on cortical bone more profoundly compared to trabecular bone. This study demonstrates that SCA-I is more effective compared to the human calcitonin monomers on osteoclasts and has site-specific effect on bone in a model of post-menopausal osteoporosis. This approach opens up an innovative way to use and study the function of human calcitonin.

Targeted inhibition of sclerostin for post-menopausal osteoporosis therapy: A critical assessment of the mechanism of action.

Promising news in the treatment of osteoporosis is that sequestering sclerostin from circulation with antibodies stimulates robust bone formation. Pre-clinical studies on rodents and monkeys have confirmed that treatment with anti-sclerostin monoclonal antibody (Scl-Ab) increases bone mass, improves bone strength and enhances fracture repair. Clinical trials show that bone gain (anabolic effect) is transient and are primarily at central (spine and hips) than peripheral (wrist) sites. Interestingly Scl-Ab also inhibited bone resorption. Thus Scl-Ab is being regarded as the pharmacologic agent with dual properties - stimulating bone formation and decreasing bone resorption. Sclerostin neutralization transiently increases bone formation markers in post-menopausal women and like parathyroid hormone (PTH) activates osteoblasts and lining cells resulting in bone anabolic effect. However, unlike PTH, sclerostin antibody also decreases bone resorption (anti-catabolic). Although, the U.S. Food and Drug Administration have accepted the Biologics License Application for one of the monoclonal antibodies against sclerostin (romosozumab) for review, many questions remain before romosozumab can be introduced as a skeletal anabolic agent to clinical practice. For example, neutralizing sclerostin alters calcium homeostasis and increases PTH. In addition, sclerostin depletion in preclinical studies has been reported to severely compromises B cell depletion in bone marrow. We have reviewed the currently available evidences that support the use of sclerostin antibody in treating osteoporosis and compare its efficacy and mechanism of action with the currently available anabolic drug, human PTH.

Tracking the Progression of Osteolytic and Osteosclerotic Lesions in Mice Using Serial In Vivo µCT: Applications to the Assessment of Bisphosphonate Treatment Efficacy.

The metastasis of tumor cells to bone can lead to osteolytic and osteosclerotic lesions, which cause severe, highly-localized bone destruction and abnormal bone apposition, respectively. Accurate quantification of lesion progression is critical to understand underlying mechanisms and assess treatment efficacy; however, standard structural parameters may be insensitive to local changes. We developed methods to quantify osteolytic and osteosclerotic lesions using micro-computed tomography (µCT) within in vivo mouse datasets. Two Balb/c nude datasets were used: (i) bone-homing MDA-MB-231 (osteolytic) cells injected into the left ventricle, treatment with alendronate or vehicle, and weekly µCT (proximal tibia) for 4 weeks, and (ii) MCF7 (osteosclerotic) cells injected into the right tibia and weekly µCT over 12 weeks. After registering images to baseline, osteolytic lesion volume was determined by summing all baseline bone voxels at distances greater than a threshold (150 µm) from the nearest follow-up. Osteosclerotic lesions were determined by measuring the distance from each follow-up surface voxel to the nearest baseline surface and calculating the standard deviation of distance values (SDDT) of the surrounding voxels. Bone mineral density (BMD), bone volume density (BV/TV), and separation (Sp) were determined for comparison. Osteolytic lesions were observed 1 week after tumor cell injection; however, no corresponding BV/TV losses or Sp increases were observed, indicating that standard parameters were unable to detect early metastatic changes. Lesion volume was smaller in the alendronate versus control group (15.0%, p = 0.004 and 18.6%, p = 0.002 of control lesion volume at weeks 3 and 4, respectively). In the osteosclerotic dataset, increased SDDT was observed following injection, providing a potential new measure of osteosclerotic bone apposition. These data show that quantification of local structural change with serial µCT may overcome the limitations of standard mineral and microstructural parameters, and successfully separates metastatic and normal bone turnover. © 2017 American Society for Bone and Mineral Research.

Pharmacologically Inactive Bisphosphonates as an Alternative Strategy for Targeting Osteoclasts: In Vivo Assessment of 5-Fluorodeoxyuridine-Alendronate in a Preclinical Model of Breast Cancer Bone Metastases.

Bisphosphonates have effects that are antiresorptive, antitumor, and antiapoptotic to osteoblasts and osteocytes, but an effective means of eliciting these multiple activities in the treatment of bone metastases has not been identified. Antimetabolite-bisphosphonate conjugates have potential for improved performance as a class of bone-specific antineoplastic drugs. The primary objective of the study was to determine whether an antimetabolite-bisphosphonate conjugate will preserve bone formation concomitant with antiresorptive and antitumor activity. 5-FdU-ale, a highly stable conjugate between the antimetabolite 5-fluoro-2'-deoxyuridine and the bisphosphonate alendronate, was tested for its therapeutic efficacy in a mouse model of MDA-MB231 breast cancer bone metastases. In vitro testing revealed osteoclasts to be highly sensitive to 5-FdU-ale. In contrast, osteoblasts had significantly reduced sensitivity. Tumor cells were resistant in vitro but in vivo tumor burden was nevertheless significantly reduced compared with untreated mice. Sensitivity to 5-FdU-ale was not mediated through inhibition of farnesyl diphosphate synthase activity, but cell cycle arrest was observed. Although serum tartrate-resistant acid phosphatase (TRAP) levels were greatly reduced by both drugs, there was no significant decrease in the serum bone formation marker osteocalcin with 5-FdU-ale treatment. In contrast, there was more than a fivefold decrease in serum osteocalcin levels with alendronate treatment (p < 0.001). This finding is supported by time-lapse micro-computed tomography analyses, which revealed bone formation volume to be on average 1.6-fold higher with 5-FdU-ale treatment compared with alendronate (p < 0.001). We conclude that 5-FdU-ale, which is a poor prenylation inhibitor but maintains potent antiresorptive activity, does not reduce bone formation and has cytostatic antitumor efficacy. These results document that conjugation of an antimetabolite with bisphosphonates offers flexibility in creating potent bone-targeting drugs with cytostatic, bone protection properties that show limited nephrotoxicity. This unique class of drugs may offer distinct advantages in the setting of targeted adjuvant therapy and chemoprevention of bone diseases. © 2016 American Society for Bone and Mineral Research.

Glenoid bone loss: assessment with MR imaging.

PURPOSE: To investigate the agreement among magnetic resonance (MR) imaging, computed tomography (CT), and arthroscopy in the measurement of glenoid bone loss. MATERIALS AND METHODS: This study was approved by the institutional ethics committee. One hundred seventy-six patients (158 male and 18 female patients; mean age, 26.8 years ± 12.3) with anterior shoulder dislocation underwent both shoulder MR imaging and CT examination. Anterior straight line length, glenoid width, and best-fit bone loss were measured with MR imaging and CT. Sixty-five patients also underwent arthroscopy, which was used as the standard of reference. Assessment of glenoid bone loss at MR imaging was compared with that at CT and arthroscopy. Inter- and intrareader reproducibility of MR imaging-derived measurements of glenoid bone loss was evaluated. RESULTS: There was excellent correlation between CT and MR imaging with regard to anterior straight line length (r = 0.97, P < .0001), glenoid width (r = 0.95, P < .0001), and severity of glenoid bone loss-particularly with use of best-fit circle width (r = 0.83, P < .0001) rather than best-fit circle area (r = 0.82, P < .0001). In the assessment of glenoid bone loss, the correlation between CT and arthroscopy (r = 0.91, P < .0001) was marginally better than that between MR imaging and arthroscopy (r = 0.84, P < .0001). The inter- and intrareader correlations of MR imaging-derived measurements of glenoid bone loss were excellent (R = 0.90-0.95). CONCLUSION: MR imaging assessment of glenoid bone loss, particularly with use of glenoid width, is almost as accurate as CT assessment.

Three-dimensional assessment of mandibular and glenoid fossa changes after bone-anchored Class III intermaxillary traction.

INTRODUCTION: Conventional treatment for young Class III patients involves extraoral devices designed to either protract the maxilla or restrain mandibular growth. The use of skeletal anchorage offers a promising alternative to obtain orthopedic results with fewer dental compensations. Our aim was to evaluate 3-dimensional changes in the mandibles and the glenoid fossae of Class III patients treated with bone-anchored maxillary protraction. METHODS: Twenty-five consecutive skeletal Class III patients between the ages of 9 and 13 years (mean age, 11.10 ± 1.1 year) were treated with Class III intermaxillary elastics and bilateral miniplates (2 in the infrazygomatic crests of the maxilla and 2 in the anterior mandible). The patients had cone-beam computed tomography images taken before initial loading and at the end of active treatment. Three-dimensional models were generated from these images, registered on the anterior cranial base, and analyzed by using color maps. RESULTS: Posterior displacement of the mandible at the end of treatment was observed in all subjects (posterior ramus: mean, 2.74 ± 1.36 mm; condyles: mean, 2.07 ± 1.16 mm; chin: mean, -0.13 ± 2.89 mm). Remodeling of the glenoid fossa at the anterior eminence (mean, 1.38 ± 1.03 mm) and bone resorption at the posterior wall (mean, -1.34 ± 0.6 mm) were observed in most patients. CONCLUSIONS: This new treatment approach offers a promising alternative to restrain mandibular growth for Class III patients with a component of mandibular prognathism or to compensate for maxillary deficiency in patients with hypoplasia of the midface. Future studies with long-term follow-up and comparisons with facemask and chincup therapies are needed to better understand the treatment effects.

Zoledronic acid : a review of its use in the management of bone metastases of malignancy.

Zoledronic acid (Zometa), a third-generation amino-bisphosphonate, has been approved in the US, the EU and many other countries worldwide for the prevention of skeletal-related events in patients with bone metastases of malignancy. In several well designed trials, zoledronic acid 4 mg administered as a 15-minute infusion every 3-4 weeks was effective in reducing the occurrence of skeletal complications in patients with bone metastases secondary to multiple myeloma, breast cancer or prostate cancer. Zoledronic acid was as effective as pamidronic acid in reducing the occurrence of skeletal complications in patients with multiple myeloma or breast cancer. In patients with solid tumours other than breast or prostate cancer, zoledronic acid did not show significant clinical benefit over placebo in terms of the primary endpoint; however, some benefit of therapy in terms of secondary endpoints was observed with zoledronic acid relative to placebo. Its efficacy in a broad range of tumours and short infusion time (15 minutes) are an advantage over other available bisphosphonates. Modelled pharmacoeconomic analyses in patients with breast cancer suggested that zoledronic acid therapy is cost effective relative to no therapy with regard to the cost per quality-adjusted life-year (QALY) gained; however, results were mixed when zoledronic acid was compared with other commonly used bisphosphonates. Zoledronic acid is generally well tolerated; the risk of osteonecrosis of the jaw may be minimized by adhering to recommendations regarding dental therapy. Additional efficacy and economic data are required to definitively position zoledronic acid with respect to other bisphosphonates. Nevertheless, available clinical data indicate that zoledronic acid is an effective treatment option for the management of bone metastases of malignancy.

Comparative assessment of bone mass and structure using texture-based and histomorphometric analyses.

The purpose of this study was to develop a methodology for quantitatively assessing bone quantity and anisotropy based on texture analysis using Gabor wavelets. The wavelet approach has the capability to simultaneously examine the images at low and high resolutions to gain information on both global and detailed local features of the bone image. The program that implemented the texture analysis gave measures of density (M(Density)) and anisotropy (M(Anisotropy)). It also allowed us to examine the texture energy at four orientations (0 degrees , 45 degrees , 90 degrees , 135 degrees) to gain insight about the details of the anisotropy. Analysis of templates of four simulated patterns, which had same number of dots but with differing orientations, demonstrated how the texture-based analysis differentiated between these templates. The measures of M(Anisotropy) discriminated between the four simulated patterns. The M(Density) measures were similar across all patterns. These outcomes matched the design intent of the simulated patterns. We also compared the trabecular bone images obtained from a previous study, in which the right forelimbs of normal female retired breeder beagle dogs (5-7 years old) were cast for 12 months to induce bone loss, using both histomorphometry and texture analysis. Both histomorphometry and the texture analysis detected significant differences in the trabecular bone of the distal metatarsal between the control and disuse groups. Percent trabecular bone (Tb.Ar/T.Ar) and the textural density parameter (M(Density)) were highly correlated (r=0.962). M(Anisotropy) was decreased (3.9%) after the 12-month disuse protocol, but was not significantly different from normal. However, the texture energy values at all orientations (0 degrees , 45 degrees , 90 degrees and 135 degrees) were significantly decreased in the disuse group. Therefore, texture analysis was able to assess anisotropy, which could not be extracted from histomorphometric parameters. We conclude that texture analysis is an effective tool for assessing 2D bone images that yields information regarding the quantity of bone as well as the orientation of the trabecular structure that can augment our ability to discriminate between normal and pathological bone tissue.

Inaccuracies inherent in dual-energy X-ray absorptiometry in vivo bone mineral densitometry may flaw osteopenic/osteoporotic interpretations and mislead assessment of antiresorptive therapy effectiveness.

New, anatomically realistic simulation studies based on a cadaveric lumbar vertebra and a broad range of soft tissue anthropometric representations have quantitatively delineated inaccuracies inherent in dual-energy X-ray absorptiometry (DXA) in vivo bone mineral density (BMD) methodology. It is found that systematic inaccuracies in DXA BMD measurements may readily exceed +/-20% at typical in vivo lumbar vertebral sites, especially for osteopenic/osteoporotic, postmenopausal, and elderly patients. These findings are quantitatively compared with extensive clinical evidence of strong, positive correlations between soft tissue anthropometrics and DXA in vivo BMD upon which prior significant bone biology interpretations and implications have been based. The agreement is found to be both qualitatively and quantitatively excellent. Moreover, recent extensive multicenter clinical studies have also exposed new facets of strong linkages between body mass/percent body fat/body mass index (BMI) and DXA-measured BMD that are particularly relevant to osteopenia/osteoporosis and remedial effectiveness of antiresorptive drug therapy. These seemingly disparate and unrelated diagnostic and prognostic aspects of clinically observed associations between soft tissue anthropometrics and measured vertebral BMD are, in this study, self-consistently shown to share the common origin of being manifestations of systematic inherent inaccuracies in DXA in vivo BMD methodology, without the need to invoke any underlying biologically causal mechanism(s). These inaccuracies arise principally from absorptiometric disparities between the intra- and extraosseous soft tissues within the DXA scan region of interest. The present evaluative comparisons are based exclusively on an incisive and diverse body of clinical data that appears difficult to dismiss or discount. Previous invocations of biologically causal mechanisms responsible for this broad range of observations linking body mass, percent body fat, and/or BMI to measured BMD now appear questionable. This doubtful status has also been extended in the present work to previously reported relationships between antiresorptive therapies and observed changes in DXA-derived BMD. These findings strongly indicate that critical and insightful reassessments of diagnostic/prognostic imputations underpinned by DXA in vivo BMD measurements are warranted. It is suggested that a good deal of what is known of bone fragility, bone densitometry, antiresorptive drug efficacy, and/or other therapeutic regimens, if based on patient-specific in vivo DXA methodology, may prove to be equivocal and tenuous.

Histomorphometric assessment of bone changes in rats with type II collagen-induced arthritis.

Numerous studies have demonstrated bone loss in rats following immobilization by tenotomy or nerve sectioning and following ovariectomy. However, few experiments have focused on bone change in rats with arthritis. We investigated bone loss in the proximal tibia and lumbar vertebra in rats with type II collagen-induced arthritis, an experimental model of rheumatoid arthritis, using histomorphometry. Bone loss in the early phase after immunization reflected a significant increase in numbers of osteoclasts and temporarily decreased bone formation. In the proximal tibia, near an arthritic joint, osteoclast numbers associated with bone trabeculae were increased four times over control numbers 4 weeks after immunization. In the lumbar vertebra, where arthritis was not shown, recruitment of osteoclasts occurred later than in the proximal tibia. With time, in both the proximal tibia and lumbar vertebra bone resorption normalized, but bone formation rate and double-label surface by tetracycline, a parameter reflecting bone formation, were increased above control values. We conclude that differences between the proximal tibia and lumbar vertebra probably reflected resumption of function as well as distance from areas of inflammation. These findings indicate that collagen-induced arthritis in rats is a useful model not only of autoimmunity, but also of juxta-articular and generalized osteoporosis in rheumatoid arthritis.

Quantitative assessment of vertical heights of maxillary and mandibular bones in panoramic radiographs of elderly dentate and edentulous subjects.

The clinical applicability of vertical measurements of the mandible and maxilla in panoramic radiographs was studied by assessing the variety of vertical heights among 91 elderly dentate subjects. Measurements in each jaw and calculations of a maxillary ratio were made at five sites. Variations in measurements of the dentate subjects were small: 9-11% for vertical measurements in the mandible, 6-11% for vertical measurements in the maxilla, and 8-10% for the maxillary ratios. These findings suggest that it is possible quantitatively to assess heights of the mandibular and maxillary bones in panoramic radiographs. Reductions in the edentulous jaws were assessed by comparing the heights of jaws of elderly dentate subjects with those measured in 177 elderly edentulous subjects. Significant differences in heights of the mandibular body and maxilla were found between the dentate and the edentulous (P < 0.001). Edentulous women had greater values for percentage reduction in the mandibles than did the men (P < 0.01; P < 0.001 in various locations).

A pharmacological assessment of the mammalian osteoclast vacuolar H(+)-ATPase.

It is well established that osteoclasts use a vacuolar-type H(+)-ATPase (V-ATPase) for proton pumping during bone resorption and that specific V-ATPase inhibitors such as bafilomycin A1 abolish osteoclastic bone resorption in the bone slice assay. It has been reported that the V-ATPase in avian osteoclasts can be distinguished from the V-ATPase expressed in most other cells, by virtue of its inhibition by vanadate and nitrate ions. In order to determine whether the V-ATPase in mammalian osteoclasts can be similarly distinguished, we have investigated the effects of vanadate and nitrate on bone resorption by rat osteoclasts in the bone slice assay, in comparison with known V-ATPase inhibitors, bafilomycin A1 and WY 47766, that also inhibit the chicken osteoclast V-ATPase. The results indicate that, unlike the avian osteoclast V-ATPase, the mammalian osteoclast V-ATPase is pharmacologically similar to the V-ATPase in other cells.

An assay system utilizing devitalized bone for assessment of differentiation of osteoclast progenitors.

The present study provides a novel assay system to examine the differentiation of osteoclast progenitors on devitalized bone slices. We used the population of bone cells liberated enzymatically from 14-day-old mouse embryonal calvariae as a source of osteoclast progenitors. The analysis of differentiation of osteoclast progenitors into preosteoclasts and mature osteoclasts was assessed in terms of the formation of TRAP-positive cells and pits or resorption lacunae, respectively, on devitalized bone slices. Osteoclasts having bone-resorbing activity appeared when the calvarial cell population was cultured in the presence of 1 alpha,25-(OH)2D3 on devitalized bone slices. The resorbing activity increased in a 1 alpha,25-(OH)2D3 dose-related manner. However, calcitonin, a potent inhibitor of differentiation and activation of osteoclast lineage cells, reduced the area of the resorption lacunae in a dose-dependent fashion. The bone-resorbing cells on the bone slices expressed an obvious ruffled border and clear zone, structures specific to mature osteoclasts. These results suggest that osteoclast progenitors in the mouse calvarial population examined differentiated into mature osteoclasts in the presence of 1 alpha,25-(OH)2D3 on devitalized bone slices. Further, using this assay system we assessed the effect of some other osteotropic factors on the differentiation of osteoclast progenitors to mature osteoclasts. IL-1, IL-6, and PTH increased the formation of TRAP-positive cells and pits and the area of resorption lacunae in a dose-dependent fashion. However, prostaglandin E2 was unable to induce the formation of resorption lacunae, although a significant appearance of TRAP-positive cells was observed at a concentration of 200 ng/ml.(ABSTRACT TRUNCATED AT 250 WORDS)

A model for decision making regarding periodontal treatment needs.

The aim of this study was to present a tentative model for decision making regarding periodontal treatment needs, based on the amount of remaining periodontal bone support. In the model presented, a maintained alveolar bone height of one third of the root length at the age of 75 years was regarded to be a reasonable goal. The data analyzed were derived from a patient sample of 194 dentate individuals aged 25-70 years from whom 2 full mouth series of intraoral radiographs, approximately 10 years apart, were available. For teeth present at both examinations, the radiographs were evaluated with respect to alveolar bone levels at the mesial and distal aspect of the teeth, i.e., the distance between the cemento-enamel junction and the most coronal level of the bone support. Longitudinal alveolar bone level change was determined for each tooth site and the alteration in alveolar bone height per 5-year interval between 25 and 75 years of age was described. Based on the calculated mean bone loss data, a rate factor was determined for each tooth site and used in the final description of the alveolar bone level for each particular tooth site at ages 30, 35, 40, ..., and 70 years, depicting the amount of bone loss beyond which therapeutic intervention has to be made in order to meet the defined goal of the tentative model. The relevance of the model and its applicability are discussed.

Periodontal alterations in patients with pemphigus vulgaris taking steroids. A biannual assessment.

Periodontal health parameters and salivary cortisol were studied in 19 adult pemphigus vulgaris patients on chronic steroid therapy. The patient population was divided into non-medicated and medicated subjects at intake into the study. A significant difference between the 2 examinations, performed at an interval of 8.73 months +/- 4.35, was found in bleeding index (p less than 0.000 and p less than 0.04, respectively) and gingival recession (p less than 0.000 and p less than 0.009) in both groups. No changes occurred in alveolar bone height. Steroid therapy altered the bleeding index (R = 0.60 and R = 0.80) and gingival recession (R = 0.87 and 0.91) in a dose-related manner, and induced low salivary cortisol. The findings of this study would suggest suppression of the host inflammatory reaction, resulting in an alleged healthy clinical appearance of the periodontium.

A computerised technique for the quantitative assessment of resorption cavities in trabecular bone.

A computerised technique is described for the quantitative assessment of resorption cavities in iliac trabecular bone. Using an Ibas II image analyser, the original bone surface, eroded by bone resorbing cells, is reconstructed using a curve fitting technique that maintains a smooth continuity with the trabecular bone on either side of the cavity. Resorption depths are measured using an interactive elastic circle; all identified cavities are measured regardless of whether or not resorption is complete, and the measurements made include mean and maximum cavity depth, cavity length, area, and adjacent trabecular widths. Results in 13 normal subjects are presented. The technique is reproducible, simple to operate, relatively rapid, and can be applied to less sophisticated image analysis systems.