Search

High-resolution peripheral quantitative computed tomography (HR-pQCT) is a powerful tool to assess bone health. To determine how an individual's or population of interest's HR-pQCT outcomes compare to expected, reference data are required. This study provides reference data for HR-pQCT measures acquired in a population of White adults., Purpose: To provide age- and sex-specific reference data for high-resolution peripheral quantitative computed tomography (HR-pQCT) measures of the distal and diaphyseal radius and tibia acquired using a second-generation scanner and percent-of-length offsets proximal from the end of the bone., Methods: Data were acquired in White adults (aged 18-80 years) living in the Midwest region of the USA. HR-pQCT scans were performed at the 4% distal radius, 30% diaphyseal radius, 7.3% distal tibia, and 30% diaphyseal tibia. Centile curves were fit to the data using the LMS approach., Results: Scans of 867 females and 317 males were included. The fitted centile curves reveal HR-pQCT differences between ages, sexes, and sites. They also indicate differences when compared to data obtained by others using fixed length offsets. Excel-based calculators based on the current data were developed and are provided to enable computation of subject-specific percentiles, z-scores, and t-scores and to plot an individual's outcomes on the fitted curves. In addition, regression equations are provided to convert estimated failure load acquired with the conventional criteria utilized with first-generation scanners and those specifically developed for second-generation scanners., Conclusion: The current study provides unique data and resources. The combination of the reference data and calculators provide clinicians and investigators an ability to assess HR-pQCT outcomes in an individual or population of interest, when using the described scanning and analysis procedure. Ultimately, the expectation is these data will be expanded over time so the wealth of information HR-pQCT provides becomes increasingly interpretable and utilized., (© 2021. International Osteoporosis Foundation and National Osteoporosis Foundation.)

We evaluated the association between prevalent vertebral fractures and bone micro-architecture and strength measured using HR-pQCT in postmenopausal women with a recent non-vertebral fracture visiting the Fracture Liaison Service. The presence and severity of prevalent vertebral fracture reflect generalized bone deterioration., Introduction: We evaluated the association between prevalent vertebral fractures (VFs) and bone micro-architecture and strength measured using HR-pQCT in postmenopausal women visiting the Fracture Liaison Service., Methods: In this cross-sectional study in women aged 50-90 with a recent non-vertebral fracture (NVF), VFs were identified on lateral spine images by dual-energy X-ray absorptiometry. Bone micro-architecture and strength were measured at the non-dominant distal radius and distal tibia using HR-pQCT. Linear regression analyses were used to estimate the association between prevalent VFs and HR-pQCT parameters., Results: We included 338 women of whom 74 (21.9%) women had at least one prevalent VF. After adjustment for femoral neck aBMD (FN aBMD) and other parameters, women with at least one prevalent vertebral fracture had significantly lower total and trabecular vBMD and trabecular number (β - 16.7, - 11.8, and - 7.8 in the radius and - 21.4, - 16.6, and - 7.2 in the tibia, respectively), higher trabecular separation at the radius and tibia (β 9.0 and 9.3, respectively), and lower cortical thickness and calculated ultimate failure load and compressive bone strength at the tibia (β - 5.9, - 0.6, and - 10.9, respectively) as compared with those without prevalent VFs. Furthermore, more severe prevalent VFs were associated with even lower total and trabecular vBMD and lower ultimate failure load and compressive stiffness at the radius and tibia, and lower trabecular number and higher trabecular separation at the radius., Conclusion: This study indicates that the presence and severity of prevalent VFs reflect generalized bone deterioration in women with a recent NVF, independently of FN aBMD.

Horses are precocial animals and able to stand and walk within hours after birth. To cope with associated loading, intrauterine bone development has shown to be anticipative. This study provides further insight into the post-natal development of structurally important features of trabecular and subchondral bone of the talus and sagittal ridge of the tibia of warm-blooded horses. In all areas studied, the average bone volume fraction showed a gradual increase over time, which was the result of a significant increase in trabecular thickness, without significant changes in the degree of anisotropy. Similar to the mineralised part of the bone, collagen content, measured as average retardation using polarised light microscopy, increased significantly, but the degree of anisotropy of the collagen type I network did not. At birth, the subchondral bone layer had a more trabecular aspect, gradually changing to an even surface with only a few vascular canals at an age of 2 months. Presented results indicate the necessity for a stronger structure, but not for a different structural design after birth, providing further evidence for anticipatory bone development in the horse. More knowledge about the strategies used to cope with mechanical loading after birth might be helpful in understanding the developmental bone and joint diseases., (© 2018 Blackwell Verlag GmbH.)

Micro-Finite Element (micro-FE) analysis is now widely used in biomedical research as a tool to derive bone mechanical properties as they relate to its microstructure. With the development of in vivo high-resolution peripheral quantitative CT (HR-pQCT) scanners, it can now be applied to analyze bone in-vivo in the peripheral skeleton. In this survey, the results of several experimental and clinical studies are summarized that addressed the feasibility of this approach to predict bone strength in-vivo. Specific questions that will be addressed are: how accurate are strength predictions based on micro-FE; how reproducible are the results; and, is it a better predictor of bone fracture risk than DXA based measures? Based on results of experimental studies, it is first concluded that micro-FE based on HR-pQCT images can accurately predict the strength of the distal radius during a fall on the outstretched hand using either linear elastic analysis, implementing a 'Pistoia criterion' or similar criterion in combination with an 'effective' Young's modulus or using non-linear analyses. When evaluating results of clinical reproducibility studies, it is concluded that for single-center studies, errors at the radius are less than 4.4% and 3.7% and at the tibia less than 3.6% and 2.3% for stiffness and strength, respectively. In multicenter trials, however, these errors can be increased by some 1.8% and 1.4% for stiffness and strength, respectively. Finally, based on the results of large cohort studies, it is concluded that micro-FE calculated stiffness better separates cases from controls than bone density parameters for subjects with fragility fractures at any site, but not for subjects with only radius fractures. In this latter case, however, combinations of micro-FE derived parameters can significantly improve the separation., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

During bone remodelling, bone cells are thought to add and remove tissue at sites with high and low loading, respectively. To predict remodelling, it was proposed that bone is removed below and added above certain thresholds of tissue loading and within these thresholds, called a 'lazy zone', no net change in bone mass occurs. Animal experiments linking mechanical loading with changes in bone density or microstructure support load-adaptive bone remodelling, while in humans the evidence for this relationship at the micro-scale is still lacking. Using new high-resolution CT imaging techniques and computational methods, we quantify microstructural changes and physiological tissue loading in humans. Here, we show that bone remodelling sites in healthy postmenopausal women strongly correlate with tissue loading following a linear relationship without a 'lazy zone' providing unbiased evidence for load-driven remodelling in humans. This suggests that human and animal bones both react to loading induced remodelling in a similar fashion.

Few studies have investigated bone microarchitecture and biomechanical properties in men. This study assessed in vivo both aspects in a population of 185 men (aged 71 ± 10 years) with prevalent fragility fractures, compared to 185 controls matched for age, height, and weight, from the Structure of the Aging Men's Bones (STRAMBO) cohort. In this case-control study, areal BMD (aBMD) was measured by DXA, bone microarchitecture was assessed by high resolution (HR)-pQCT, and finite element (µFE) analysis was based on HR-pQCT images of distal radius and tibia. A principal component (PC) analysis (PCA) was used to study the association of synthetic PCs with fracture by computing their odds ratio (OR [95%CI]) per SD change. Specific associations with vertebral fracture (n = 100), and nonvertebral fracture (n = 85) were also computed. At both sites, areal and volumetric BMD, cortical thickness and trabecular number, separation, and distribution were significantly worse in cases than in controls, with differences ranging from -6% to 15%. µFE-derived stiffness and failure load were 8% to 9% lower in fractures (p < .01). No difference in load distribution was found between the two groups. After adjustment for aBMD, only differences of µFE-derived stresses, stiffness, and failure load at the tibia remained significant (p < .05). PCA resulted in defining 4 independent PCs, explaining 83% of the total variability of bone characteristics. Nonvertebral fractures were associated with PC1, reflecting bone quantity and strength at the radius (tibia) with OR = 1.64 [1.27-2.12] (2.21 [1.60-3.04]), and with PC2, defined by trabecular microarchitecture, with OR = 1.27 [1.00-1.61]. Severe vertebral fractures were associated with PC1, with OR = 1.56 [1.16-2.09] (2.21 [1.59-3.07]), and with PC2, with OR = 1.55 [1.17-2.06] (1.45 [1.06-1.98]). In conclusion, microarchitecture and biomechanical properties derived from µFE were associated with all types of fractures in men, showing that radius and tibia mechanical properties were relatively representative of distant bone site properties., (Copyright © 2011 American Society for Bone and Mineral Research.)

Assessment of bone strength at the radius by micro-finite element analysis (muFEA) has already been associated with wrist fractures. In this study, the analysis has been extended to the distal tibia, and to a larger group of subjects to examine the association with several types of fragility fractures. We have compared muFEA based on in vivo HR-pQCT measurements of BMD and microarchitecture at the radius and tibia, in a case-control study involving 101 women with prevalent fragility fracture and 101 age-matched controls, from the OFELY cohort. Areal BMD was measured by DXA at the radius and the hip. All parameters were analyzed in a principal component (PC) analysis (PCA), and associations between PCs and fractures were computed as odds ratios (OR [95% CI]) per SD change. Radius (tibia) PCA revealed three independent components explaining 76% (77%) of the total variability of bone characteristics. The first PC describing bone strength and quantity, explained 50% (46%) of variance with an OR=1.84 [1.27-2.67] (2.92 [1.73-4.93]). The second PC including trabecular microarchitecture, explained 16% (10%) of variance, with OR=1.29 [0.90-1.87] (1.11 [0.82-1.52]). The third PC related to load distribution explained 10% (20%) of variance, with OR=1.54 [1.06-2.24] (1.32 [0.89-1.96]). Moreover, at the radius, vertebral fractures were associated with trabecular microarchitecture PC with OR=1.86 [1.14-3.03], whereas nonvertebral fractures were associated with bone strength and quantity PC with OR=2.03 [1.36-3.02]. At the tibia, both vertebral (OR=2.92 [1.61-5.28]) and nonvertebral fracture (2.64 [1.63-4.27]) were associated to bone strength and quantity PC. In conclusion, muFEA parameters at the radius and tibia were associated with all types of fragility fractures. We have also shown that muFEA parameters obtained with distal tibia data were associated with prevalent fractures with a similar magnitude that with parameters obtained at the radius., (Copyright 2009 Elsevier Inc. All rights reserved.)

Daily low-amplitude, high-frequency whole-body vibration (WBV) treatment can increase bone formation rates and bone volume in rodents. Its effects vary, however, with vibration characteristics and study design, and effects on 3D bone microstructure of ovariectomized animals over time have not been documented. Our goal was to determine the effects of WBV on tibial bone of ovariectomized, mature rats over time using an in vivo micro-CT scanner. Adult rats were divided into: ovariectomy (OVX) (n = 8), SHAM-OVX (n = 8), OVX and WBV treatment (n = 7). Eight weeks after OVX, rats in the vibration group were placed on a vibrating platform for 20 min at 0.3 g and 90 Hertz. This was done 5 days a week for six weeks, twice a day. Zero, 8, 10, 12 and 14 weeks after OVX, in vivo micro-CT scans were made (vivaCT 40, Scanco Medical AG) of the proximal and diaphyseal tibia. After sacrifice, all tibiae were dissected and tested in three-point bending. In the metaphysis between 8 to 12 weeks after OVX, WBV treatment did not alter structural parameters compared to the OVX group and both groups continued to show deterioration of bone structure. In the epiphysis, structural parameters were not altered. WBV also did not affect cortical bone and its bending properties. To summarize, no substantial effects of 6 weeks of low-magnitude, high-frequency vibration treatment on tibial bone microstructure and strength in ovariectomized rats were found.

Unlabelled: Using in vivo microcomputed tomography (micro-CT), we found in parathyroid hormone (PTH)-treated osteopenic rats linear increases in cortical and trabecular, due to increased trabecular thickness and number, bone mass. Bone was formed in cavities, leading to restoral of nearly cleaved trabeculae. For the first time, effects in PTH-treated rats were analyzed longitudinally., Introduction: Our aims were to over time (1) determine changes in trabecular thickness and number after PTH, (2) compare responses to PTH between the meta- and epiphysis, (3) determine effects of PTH on mineralization and mechanical properties, (4) determine locations of new bone formation due to PTH on a microlevel, and (5) determine the predictive value of bone structural properties for gain in bone mass after PTH., Methods: Adult rats were divided into ovariectomy (OVX; n = 8), SHAM-OVX (n = 8), and OVX and PTH treatment (n = 9). Between weeks 8 and 14, PTH rats received daily subcutaneous PTH injections (60 microg/kg/day). At weeks 0, 8, 10, 12, and 14, in vivo micro-CT scans were made of the proximal and diaphyseal tibia. After sacrifice, all tibiae were tested in three-point bending., Results: PTH increased bone volume fraction linearly over time in meta- and epiphysis, accompanied by increased trabecular thickness in both and increased trabecular number only in the latter one. CT-estimated mineralization increased in trabecular and remained constant in cortical bone. Ultimate load and energy were increased and ultimate displacement and stiffness unaltered compared to SHAM rats. For those trabeculae analyzed, bone was formed initially on places where it was most beneficial for increasing their strength and later on to all surfaces.

Summary: We recruited a population-based sample of 58 males and 74 females aged 20-79 from a primary care medical practice to provide normative and descriptive data for high-resolution peripheral quantitative computed tomography (pQCT) parameters. Important effects of ageing and contrasts in the effects of sex on the micro-architecture and strength of upper and lower limb bones were revealed., Introduction: The advent of high-resolution pQCT scanners has permitted non-invasive assessment of structural data on cortical and trabecular bone., Methods: We investigated age-related changes in pQCT and finite element (FE) modelling parameters at the distal radius and distal tibia in a population-based cross-sectional study of 58 males and 74 females aged 20-79 years. Linear regression models including quadratic terms for age were used for inference., Results: Age-related changes and sex differences were generally similar for pQCT parameters at the radius and tibia. At each site, mean values for bone density, cortical thickness and trabecular micro-architecture (number, separation and thickness) were lower (trabecular separation higher) in women than men. Changes with age were most apparent for bone density and cortical thickness, which declined with age, in contrast to trabecular micro-architecture parameters which were not significantly associated with age (p > 0.05) in either sex. Cortical bone density and thickness declined faster in women than men after age 50 and trabecular bone density was consistently lower in women. FE-analysis predicted failure load decreased with age and percentage of load carried by trabecular bone increased (p < 0.05)., Conclusions: These data show contrasts in the effects of sex on the micro-architecture and strength of upper and lower limb bones with ageing. The faster decline in cortical bone thickness and density in women than men after age 50 and consistently lower trabecular bone density in women have implications for the excess risks of wrist and hip fractures in women.

Micro-finite element (micro-FE) analysis became a standard tool for the evaluation of trabecular bone mechanical properties. The accuracy of micro-FE models for linear analyses is well established. However, the accuracy of recently developed nonlinear micro-FE models for simulations of trabecular bone failure is not known. In this study, a trabecular bone specimen was compressed beyond the apparent yield point. The experiment was simulated using different micro-FE meshes with different element sizes and types, and material models based on cortical bone. The results from the simulations were compared with experimental results to study the effects of the different element and material models. It was found that a decrease in element size from 80 to 40 mum had little effect on predicted post-yield behaviour. Element type and material model had significant effects. Nevertheless, none of the established material models for cortical bone were able to predict the typical descent in the load-displacement curve seen during compression of trabecular bone.

Bisphosphonates are antiresorptive drugs commonly used to treat osteoporosis. It is not clear, however, what the influence of the time point of treatment is. Recently developed in vivo micro-computed tomographic (CT) scanners offer the possibility to study such effects on bone microstructure in rats. The aim of this study was to determine the influence of early and late zoledronic acid treatment on bone in ovariectomized rats, using in vivo micro-CT. Twenty-nine female Wistar rats were divided into the following groups: ovariectomy (OVX, n = 5), OVX and zoledronic acid (ZOL) at week 0 (n = 8), OVX and ZOL at week 8 (n = 7), and sham (n = 9). CT scans were made of the proximal tibia at weeks 0, 2, 4, 8, 12, and 16; and bone structural parameters were determined in the metaphysis. Two fluorescent labels were administered to calculate dynamic histomorphometric parameters. At week 16, all groups were significantly different from each other in bone volume fraction (BV/TV), connectivity density, and trabecular number (Tb.N), except for the early ZOL and control groups which were not significantly different for any structural parameter. After ZOL treatment at week 8, BV/TV, structure model index, Tb.N, and trabecular thickness significantly improved in the late ZOL group. The OVX and ZOL groups showed, respectively, higher and lower bone formation rates than the control group. Early ZOL treatment inhibited all bone microstructural changes seen after OVX. Late ZOL treatment significantly improved bone microstructure, although the structure did not recover to original levels. Early ZOL treatment resulted in a significantly better microstructure than late treatment. However, late treatment was still significantly better than no treatment.

Trabecular bone strength is marked not only by the onset of local yielding, but also by post-yield behavior. To study and predict trabecular bone elastic and yield properties, micro-finite element (micro-FE) models were successfully applied. However, trabecular bone strength predictions require micro-FE models incorporating post-yield behavior of trabecular bone tissue. Due to experimental difficulties, such data is currently not available. Here we used micro-FE modeling to determine failure behavior of trabecular bone tissue indirectly, by iteratively fitting FE simulation to experimental results. Failure parameters were fitted to an isotropic plasticity model based on Hill's yield function, using materially and geometrically nonlinear micro-FE models of seven bovine trabecular bone specimens. The predictive value of the averaged effective tissue properties was subsequently tested. The results showed that compression softening had to be included on the tissue level in order to accurately describe the apparent-level behavior of the bone specimens. A sensitivity study revealed that the simulated response was less sensitive to variations in the post-yield properties of the bone tissue than variations in the elastic and yield properties. Due to fitting of the tissue properties, apparent-level behavior could be accurately reproduced for each specimen separately. Predictions based on the averaged and fixed tissue properties were less accurate, due to inter-specimen variations in the tissue properties.

Recently developed in vivo animal high-resolution micro-CT scanners offer the possibility to monitor longitudinal changes in bone microstructure of small rodents, but may impose high radiation doses that could damage bone tissue. The goal of this study was to determine the effects on the bone of 8 weeks of in vivo scanning of the proximal tibia in female Wistar rats. Eight weekly CT scans were made of the right proximal tibia of nine female, 30-week-old, retired-breeder, Wistar rats. Two weeks after the last weekly scan, a final scan was made. The left leg was only scanned during first and final measurements and served as a control. A two-way ANOVA with repeated measures was performed on the first and last measurements of left and right tibiae for six bone structural parameters. Bone marrow cells were flushed out and tested for cell viability. No significant difference was found between left and right for any of the bone structural parameters (p > 0.05). Structure model index and trabecular separation significantly changed as a result of aging, while none of the other parameters did. No significant difference was found between left and right in absolute and percentage number of cell viability. We did not find any indication that the applied scanning regime, in combination with the particular settings used, would affect the results of in vivo bone structural measurements in long-term studies using aged, female Wistar rats. However, careful consideration should be made when determining the number of scans, particularly when a different experimental design is used.

Introduction: The aim of this study was to investigate the associations of patient characteristics, bone mineral density (BMD), bone microarchitecture and calculated bone strength with secondary displacement of a DRF based on radiographic alignment parameters.Materials and Methods: Dorsal angulation, radial inclination and ulnar variance were assessed on conventional radiographs of a cohort of 251 patients, 38 men and 213 women, to determine the anatomic position of the DRF at presentation (primary position) and during follow-up. Secondary fracture displacement was assessed in the non-operatively treated patients (N = 154) with an acceptable position, preceded (N = 97) or not preceded (N = 57) by primary reduction (baseline position). Additionally, bone microarchitecture and calculated bone strength at the contralateral distal radius and tibia were assessed by HR-pQCT in a subset of, respectively, 63 and 71 patients.Outcome: Characteristics of patients with and without secondary fracture displacement did not differ. In the model with adjustment for primary reduction [OR 22.00 (2.27-212.86), p = 0.008], total [OR 0.16 (95% CI 0.04-0.68), p = 0.013] and cortical [OR 0.19 (95% CI 0.05-0.80], p = 0.024] volumetric BMD (vBMD) and cortical thickness [OR 0.13 (95% CI 0.02-0.74), p = 0.021] at the distal radius were associated with secondary DRF displacement. No associations were found for other patient characteristics, such as age gender, BMD or prevalent vertebral fractures.Conclusions: In conclusion, our study indicates that besides primary reduction, cortical bone quality may be important for the risk of secondary displacement of DRFs. [ABSTRACT FROM AUTHOR]

Summary: A longitudinal analysis of bone microstructure in postmenopausal women of the Geneva Retirees Cohort indicates that age-related cortical bone loss is attenuated at non-bearing bone sites in fermented dairy products consumers, not in milk or ripened cheese consumers, independently of total energy, calcium, or protein intakes.Introduction: Fermented dairy products (FDP), including yogurts, provide calcium, phosphorus, and proteins together with prebiotics and probiotics, all being potentially beneficial for bone. In this prospective cohort study, we investigated whether FDP, milk, or ripened cheese consumptions influence age-related changes of bone mineral density (BMD) and microstructure.Methods: Dietary intakes were assessed at baseline and after 3.0 ± 0.5 years with a food frequency questionnaire in 482 postmenopausal women enrolled in the Geneva Retirees Cohort. Cortical (Ct) and trabecular (Tb) volumetric (v) BMD and microstructure at the distal radius and tibia were assessed by high-resolution peripheral quantitative computerized tomography, in addition to areal (a) BMD and body composition by dual-energy X-ray absorptiometry, at the same time points.Results: At baseline, FDP consumers had lower abdominal fat mass and larger bone size at the radius and tibia. Parathyroid hormone and β-carboxyterminal cross-linked telopeptide of type I collagen levels were inversely correlated with FDP consumption. In the longitudinal analysis, FDP consumption (mean of the two assessments) was associated with attenuated loss of radius total vBMD and of Ct vBMD, area, and thickness. There was no difference in aBMD and at the tibia. These associations were independent of total energy, calcium, or protein intakes. For other dairy products categories, only milk consumption was associated with lower decrease of aBMD and of failure load at the radius.Conclusion: In this prospective cohort of healthy postmenopausal women, age-related Ct bone loss was attenuated at non-bearing bone sites in FDP consumers, not in milk or ripened cheese consumers, independently of total energy, calcium, or protein intakes.Study registration: ISRCTN11865958 (http://www.isrctn.com) [ABSTRACT FROM AUTHOR]

Objectives: To introduce a fully-automated algorithm for the detection of small cortical interruptions (≥0.246mm in diameter) on high resolution peripheral quantitative computed tomography (HR-pQCT) images, and to investigate the additional value of manual correction of the automatically obtained contours (semi-automated procedure). Methods: Ten metacarpophalangeal joints from seven patients with rheumatoid arthritis (RA) and three healthy controls were imaged with HR-pQCT. The images were evaluated by an algorithm according to the fully- and semi-automated procedure for the number and surface of interruptions per joint. Reliability between the fully- and semi-automated procedure and between two independent operators was tested using intra-class correlation coefficient (ICC) and the proportion of matching interruptions. Validity of single interruptions detected was tested by comparing it to visual scoring, as gold standard. The positive predictive value (PPV) and sensitivity were calculated. Results: The median number of interruptions per joint was 14 (range 2 to 59) and did not significantly differ between the fully- and semi-automated procedure (p = 0.37). The median interruption surface per joint was significantly higher with the fully- vs. semi-automated procedure (respectively, 8.6mm2 vs. 5.8mm2 and 6.1mm2, p = 0.01). Reliability was almost perfect between the fully- and semi-automated procedure for both the number and surface of interruptions (ICC≥0.95) and the proportion of matching interruptions was high (≥76%). Also the inter-operator reliability was almost perfect (ICC≥0.97, proportion of matching interruptions 92%). The PPV ranged from 27.6% to 29.9%, and sensitivity from 69.7% to 76.3%. Most interruptions detected with the algorithm, did show an interruption on a 2D grayscale image. However, this interruption did not meet the criteria of an interruption with visual scoring. Conclusion: The algorithm for HR-pQCT images detects cortical interruptions, and its interruption surface. Reliability and validity was comparable for the fully- and semi-automated procedures. However, we advise the use of the semi-automated procedure to assure quality. The algorithm is a promising tool for a sensitive and objective assessment of cortical interruptions in finger joints assessed by HR-pQCT. [ABSTRACT FROM AUTHOR]

Abstract: During endochondral ossification, growth plate cartilage is replaced with bone. Mineralized cartilage matrix is resorbed by osteoclasts, and new bone tissue is formed by osteoblasts. As mineralized cartilage does not contain any cells, it is unclear how this process is regulated. We hypothesize that, in analogy with bone remodeling, osteoclast and osteoblast activity are regulated by osteocytes, in response to mechanical loading. Since the cartilage does not contain osteocytes, this means that cartilage turnover during endochondral ossification would be regulated by the adjacent bone tissue. We investigated this hypothesis with an established computational bone adaptation model. In this model, osteocytes stimulate osteoblastic bone formation in response to the mechanical bone tissue loading. Osteoclasts resorb bone near randomly occurring microcracks that are assumed to block osteocyte signals. We used finite element modeling to evaluate our hypothesis in a 2D-domain representing part of the growth plate and adjacent bone. Cartilage was added at a constant physiological rate to simulate growth. Simulations showed that osteocyte signals from neighboring bone were sufficient for successful cartilage turnover, since equilibrium between cartilage remodeling and growth was obtained. Furthermore, there was good agreement between simulated bone structures and rat tibia histology, and the development of the trabecular architecture resembled that of infant long bones. Additionally, prohibiting osteoclast invasion resulted in thickened mineralized cartilage, similar to observations in a knock-out mouse model. We therefore conclude that it is well possible that osteocytes regulate the turnover of mineralized growth plate cartilage. [Copyright &y& Elsevier]