Matrix Mineral Density Research Articles

Increased Osteocyte Lacunae Density in the Hypermineralized Bone Matrix of Children with Osteogenesis Imperfecta Type I.

Osteocytes are terminally differentiated osteoblasts embedded within the bone matrix and key orchestrators of bone metabolism. However, they are generally not characterized by conventional bone histomorphometry because of their location and the limited resolution of light microscopy. OI is characterized by disturbed bone homeostasis, matrix abnormalities and elevated bone matrix mineralization density. To gain further insights into osteocyte characteristics and bone metabolism in OI, we evaluated 2D osteocyte lacunae sections (OLS) based on quantitative backscattered electron imaging in transiliac bone biopsy samples from children with OI type I (n = 19) and age-matched controls (n = 24). The OLS characteristics were related to previously obtained, re-visited histomorphometric parameters. Moreover, we present pediatric bone mineralization density distribution reference data in OI type I (n = 19) and controls (n = 50) obtained with a field emission scanning electron microscope. Compared to controls, OI has highly increased OLS density in cortical and trabecular bone (+50.66%, +61.73%; both p < 0.001), whereas OLS area is slightly decreased in trabecular bone (−10.28%; p = 0.015). Correlation analyses show a low to moderate, positive association of OLS density with surface-based bone formation parameters and negative association with indices of osteoblast function. In conclusion, hyperosteocytosis of the hypermineralized OI bone matrix associates with abnormal bone cell metabolism and might further impact the mechanical competence of the bone tissue.

Effect of ionizing radiation and cariogenic biofilm challenge on root-dentin caries.

To evaluate the effect of ionizing radiation and cariogenic biofilm challenge using two continuous flow models, normal and reduced salivary flow, on the development of initial root-dentin caries lesions. Microcosm biofilms were grown under two salivary flow rates (0.06 and 0.03mLmin-1) and exposed to 5% sucrose (3 × daily, 0.25mLmin-1, 6min) dripped over non-irradiated and irradiated root-dentin blocks for up to 7days. The vibration modes of root dentin, matrix/mineral (M/M), and carbonate/mineral (C/M) ratios were evaluated by FTIR. The mineral density was assessed by micro-CT. With normal salivary flow, FTIR revealed an increase in the organic matrix (amide III) and a decrease in the mineral phase (ν4, ν2 PO43-, AII + ν2 CO32-, C/M) in caries lesions. Irradiated dentin exhibited a reduction in the mineral phase (ν1, ν3 PO43-, ν2 CO32-, C/M). Differences in mineral densities were not significant. With reduced salivary flow, FTIR also revealed increased organic matrix (amide III) for irradiated caries lesions and decrease in mineral phase (v4, v2 PO43-, v2 CO32-, and C/M) in caries lesions. ν1, ν3 PO43- precipitated on the surface of irradiated dentin and a lower mineral density was observed. Initial caries lesions differed between non-irradiated and irradiated dentin and between normal and reduced salivary flow rates. Significant mineral loss with exposure of the organic matrix and low mineral density were observed for irradiated dentin with a reduced salivary flow rate. Ionizing radiation associated with a reduced salivary flow rate enhanced the progression of root-dentin caries.

Dimorphism in axial and appendicular dimensions, cortical and trabecular microstructure and matrix mineral density in Chinese and Caucasian women.

Appendicular fractures are less common in Chinese than Caucasian women. Bone mineral density (BMD) is lower, not higher than in Caucasians because Chinese have smaller appendicular dimensions than Caucasians. However, smaller bones may offset the liability to fracture by being assembled with a more robust microstructure. We hypothesized that Chinese assemble an appendicular skeleton with a thicker, less porous and more mineralized cortex that is less deteriorated in advanced age than in Caucasians. We compared anthropometry in 477 Chinese and 278 Caucasian women and compared bone microstructure using high-resolution peripheral quantitative computed tomography in another cohort of 186 Chinese and 381 Caucasian women aged 18 to 86 years, all living in Melbourne, Australia. Trabecular plate (p) and rod (r) bone volume/total volume (BV/TV) were quantified using individual trabecula segmentation (ITS). Bone strength was estimated using micro-finite element analysis (μFEA). Premenopausal Chinese were shorter than Caucasian women, mainly due to shorter leg length. Distal radial total cross sectional area (CSA) was 14.8% smaller (p < 0.001). After adjusting for age and total CSA, Chinese had similar cortical and medullary areas but 0.30 SD lower cortical porosity and 0.27 SD higher matrix mineral density (both p < 0.05). Trabecular plate-to-rod ratio was 0.55 SD higher due to a 0.41 SD higher pBV/TV and 0.36 SD lower rBV/TV (p ranging 0.001 to 0.023). Chinese also had 0.36 SD greater whole bone stiffness and 0.36 SD greater failure load than Caucasians (both p < 0.05). After adjusting for age and total CSA, postmenopausal Chinese had 3.3% smaller cortical area, medullary area was 2.1% larger, cortical porosity was no lower, matrix mineral density and pBV/TV were no higher compared with Caucasians at the distal radius. Whole bone stiffness was 0.39 SD lower and failure load was 0.40 SD lower in Chinese (both p < 0.05). Chinese build a more robust skeleton than Caucasians during growth, an advantage not observed in advanced age due to greater bone loss or race-specific secular trends in bone morphology.

Advances and Unmet Needs in the Therapeutics of Bone Fragility.

The prevalence of fragility fractures increases as longevity increases the proportion of the elderly in the community. Until recently, the majority of studies have targeted women with osteoporosis defined as a bone mineral density (BMD) T score of < −2.5 SD, despite evidence that the population burden of fractures arises from women with osteopenia. Antiresorptive agents reduce vertebral and hip fracture risk by ~50 percent during 3 years but efficacy against non-vertebral fractures, 80% of all fractures in the community, is reported in few studies, and of those, the risk reduction is only 20–30%. Recent advances in the use of antiresorptives and anabolic agents has addressed some of these unmet needs. Zoledronic acid is now reported to reduce vertebral and non-vertebral fractures rates in women with osteopenia. Studies using teriparatide demonstrate better vertebral and clinical (symptomatic vertebral and non-vertebral) antifracture efficacy than risedronate. Abaloparatide, a peptide sharing amino acid sequences with teriparatide, reduces vertebral and non-vertebral fractures. Romosozumab, a monoclonal antibody suppressing sclerostin, reduces vertebral and non-vertebral fractures within a year of starting treatment, and does so more greatly than alendronate. Some recent studies signal undesirable effects of therapy but provide essential cautionary insights into long term management. Cessation of denosumab is associated with a rapid increase in bone remodeling and the uncommon but clinically important observation of increased multiple vertebral fractures suggesting the need to start alternative anti-resorptive therapy around the time of stopping denosumab. Antiresorptives like bisphosphonates and denosumab suppress remodeling but not completely. Antifracture efficacy may be limited, in part, as a consequence of continued unsuppressed remodeling, particularly in cortical bone. Bisphosphonates may not distribute in deeper cortical bone, so unbalanced intracortical remodeling continues to cause microstructural deterioration. In addition, suppressed remodeling may compromise the material composition by increasing matrix mineral density and glycosylation of collagen. As antiresorptive agents do not restore microstructural deterioration existing at the time of starting treatment, under some circumstances, anabolic therapy may be more appropriate first line treatment. Combining antiresorptive and anabolic therapy is an alternative but whether anti-fracture efficacy is greater than that achieved by either treatment alone is not known.

Sexual Dimorphism in Cortical and Trabecular Bone Microstructure Appears During Puberty in Chinese Children.

Distal forearm fractures during growth are more common in males than females. Because metaphyseal cortical bone is formed by coalescence of trabeculae emerging from the periphery of the growth plate, we hypothesized that the later onset of puberty in males produces a longer delay in trabecular bone formation and coalescence, which leaves a transient phase of high cortical porosity, low matrix mineral density, and high trabecular density relative to females. We quantified the nondominant distal radial microstructure using high-resolution peripheral quantitative computed tomography in 214 healthy Chinese boys and 219 Chinese girls aged between 7 and 17 years living in Hong Kong. Measurements of 110 slices (9.02 mm) were acquired 5 mm proximal to the growth plate of the nondominant distal radius. Porosity was measured using StrAx1.0 (Straxcorp, Melbourne, VIC, Australia) and trabecular plate and rod structure were measured using individual trabecula segmentation (ITS). Mechanical properties were estimated using finite element analysis (FEA). Results were adjusted for age, total bone cross-sectional area (CSA), dietary calcium intake, and physical activity. In boys, total bone CSA was 17.2% to 22.9% larger throughout puberty, cortical/total bone CSA was 5.1% smaller in Tanner stage 2 only, cortical porosity was 9.4% to 17.5% higher, and matrix mineral density was 1.0% to 2.5% lower in Tanner stage 2 to 5, than girls. Boys had higher trabecular rod BV/TV in Tanner stage 3 and 4, but higher trabecular plate BV/TV and plate to rod ratio in Tanner stage 5, than girls. Boys had 17.0% lower apparent modulus than girls in Tanner stage 2. A transient phase of higher porosity due to dissociation between bone mineral accrual and linear growth may contribute to higher distal radial bone fragility in Chinese boys compared to girls. © 2018 American Society for Bone and Mineral Research.

Increased bone matrix mineralization in treatment-naïve children with inflammatory bowel disease

Inflammatory bowel disease (IBD) affects many organ systems including the skeleton. In children with IBD, bone mineral density (BMD) and bone turnover are frequently low. Disturbances in bone mineralization density distribution (BMDD) are linked to alterations in bone material strength; however, BMDD has not previously been reported in children with chronic inflammatory disorders. The aim of this study was to characterize BMDD based on quantitative backscatter electron imaging in cancellous (Cn.) and cortical (Ct.) compartments from trans-iliac biopsy samples from a cohort of 20 treatment-naïve children at the time of their IBD diagnosis (12 males, mean age 14.5±2.3years). The outcomes were compared to pediatric reference BMDD data and correlation with revisited biochemical and histomorphometric outcomes was analyzed.BMDD in treatment-naïve children with IBD was shifted toward higher calcium concentrations compared to reference: (i) In cancellous bone, the most frequent calcium concentration (Cn.CaPeak+2.8%, p=0.004) and the portion of highly mineralized bone (Cn.CaHigh+52%, p=0.009) were increased. (ii) In cortical bone, the mineralization heterogeneity (Ct.CaWidth+17.0%, p=0.001) and Ct.CaHigh (+30.4%, p=0.006) were increased. (iii) Furthermore, significant correlations with serum alkaline phosphatase (ALP), bone-specific alkaline phosphatase (bsALP), and urinary crosslinked N-telopeptide of type I collagen (uNTX) were observed: the higher CaMean (the average calcium concentration), CaPeak and CaHigh, the lower were ALP, bsALP, and uNTX (p-value from <0.001 to 0.05).Children with treatment-naïve IBD have decreased bone turnover leading to a higher bone matrix mineralization density, findings which may contribute to compromised bone strength.

Premenopausal women with early breast cancer treated with estradiol suppression have severely deteriorated bone microstructure

BackgroundIn premenopausal women with early estrogen-receptor-positive breast cancer, combined ovarian suppression and aromatase inhibition reduce estradiol production precipitously. The resulting unbalanced and rapid bone remodelling replaces older bone with less bone that is less fully mineralized. We hypothesized that these changes result in severe microstructural deterioration and reduced matrix mineralization density. MethodsImages of the distal radius and distal tibia were acquired using high-resolution peripheral quantitative computed tomography in a cross-sectional study of 27 premenopausal women, mean age 43.3years (range 30.4 to 53.7) with early breast cancer made estradiol deficient for 17months (range 6–120) using ovarian suppression and aromatase inhibition, 42 healthy age-matched premenopausal and 35 postmenopausal controls, mean age 62.6years (range 60.2 to 65.5). Cortical and trabecular microstructure were quantified using Strax software. ResultsCompared with premenopausal controls, the women with breast cancer had 0.75 SD (95% CI 0.21 to 1.29) lower distal radial trabecular bone volume due to 1.29 SD (0.71 to 1.87) fewer trabeculae. Cortical porosity was 1.25 SD (0.59 to 1.91) higher but cortical thickness was not reduced. Compared with postmenopausal controls 20years older, cases had comparable or lower trabecular bone volume and comparable cortical porosity and thickness. Matrix mineral density was 1.56 SD (0.90 to 2.22) lower than in premenopausal controls and 2.17 SD (1.50 to 2.84) lower than in postmenopausal controls. Results at the tibia were similar. ConclusionThe severe cortical porosity and trabecular deterioration associated with estradiol depletion and the longevity of premenopausal women with early breast cancer treated with endocrine therapy provide a compelling rationale to investigate the efficacy of antiresorptive therapy initiated at the time of breast cancer treatment.

Quantifying sex, race, and age specific differences in bone microstructure requires measurement of anatomically equivalent regions

IntroductionIndividuals differ in forearm length. As microstructure differs along the radius, we hypothesized that errors may occur when sexual and racial dimorphisms are quantified at a fixed distance from the radio-carpal joint. MethodsMicrostructure was quantified ex vivo in 18 cadaveric radii using high resolution peripheral quantitative computed tomography and in vivo in 158 Asian and Caucasian women and men at a fixed region of interest (ROI), a corrected ROI positioned at 4.5–6% of forearm length and using the fixed ROI adjusted for cross sectional area (CSA), forearm length or height. Secular effects of age were assessed by comparing 38 younger and 33 older women. ResultsEx vivo, similar amounts of bone mass fashioned adjacent cross sections. Larger distal cross sections had thinner porous cortices of lower matrix mineral density (MMD), a larger medullary CSA and higher trabecular density. Smaller proximal cross-sections had thicker less porous cortices of higher MMD, a small medullary canal with little trabecular bone. Taller persons had more distally positioned fixed ROIs which moved proximally when corrected. Shorter persons had more proximally positioned fixed ROIs which moved distally when corrected, so dimorphisms lessened. In the corrected ROIs, in Caucasians, women had 0.6 SD higher porosity and 0.6 SD lower trabecular density than men (p<0.01). In Asians, women had 0.25 SD higher porosity (NS) and 0.5 SD lower trabecular density than men (p<0.05). In women, Asians had 0.8 SD lower porosity and 0.3 SD higher trabecular density than Caucasians (p<0.01). In men, Asians and Caucasians had similar porosity and trabecular density. Results were similar using an adjusted fixed ROI. Adjusting for secular effects of age on forearm length resulted in the age-related increment in porosity increasing from 2.08 SD to 2.48 SD (p<0.05). ConclusionAssessment of sex, race and age related differences in microstructure requires measurement of anatomically equivalent regions.

Serum 25-Hydroxyvitamin D Insufficiency in Search of a Bone Disease.

Vitamin D "insufficiency" and "deficiency" are defined as serum 25-hydroxyvitamin D [25(OH)D] levels <75 and <30 nmol/L, respectively. We aimed to determine whether these values signal hypocalcemia and hypophosphatemia, secondary hyperparathyroidism, high bone remodeling, low areal bone mineral density (aBMD), microstructural deterioration, or reduced matrix mineralization density (MMD) and so suggest whether bone fragility is present. Concentrations of 25(OH)D, calcium, phosphate, creatinine, and parathyroid hormone (PTH) were measured in 11,855 participants. Serum C-terminal telopeptide of type 1 collagen, procollagen type 1 N-terminal propeptide (P1NP), aBMD, and distal radius microstructure and MMD were measured in a second subset of 150 participants. A breakpoint for calcium, PTH, and alkaline phosphatase was identified at a threshold 25(OH)D level <30 nmol/L. There was no plateau beyond 75 nmol/L. In the subgroup with measurements of bone morphology, no associations were detectable between serum 25(OH)D concentration, aBMD, trabecular density, cortical porosity, or MMD. Among 1439 participants with serum 25(OH)D <30 nmol/L, 6.1% had low serum calcium, 3.4% had low serum phosphate, 6.1% had high alkaline phosphatase, and 34.2% had elevated PTH. Most participants did not have any abnormalities. At a 25(OH)D threshold of ≤30 nmol/L, abnormalities in biochemical features support the notion of a "deficiency" state predisposing to bone disease. However, no deleterious effects were found in participants within an insufficiency threshold of a 25(OH)D level of 30 to 75 nmol/L, which challenges the rationale justifying vitamin D supplementation in these individuals.

Irreversible Deterioration of Cortical and Trabecular Microstructure Associated With Breastfeeding.

Estrogen deficiency associated with menopause is accompanied by an increase in the rate of bone remodeling and the appearance of a remodeling imbalance; each of the greater number of remodeling transactions deposits less bone than was resorbed, resulting in microstructural deterioration. The newly deposited bone is also less completely mineralized than the older bone resorbed. We examined whether breastfeeding, an estrogen-deficient state, compromises bone microstructure and matrix mineral density. Distal tibial and distal radial microarchitecture were quantified using high-resolution peripheral quantitative computed tomography in 58 women before, during, and after breastfeeding and in 48 controls during follow-up of 1 to 5 years. Five months of exclusive breastfeeding increased cortical porosity by 0.6% (95% confidence interval [CI] 0.3-0.9), reduced matrix mineralization density by 0.26% (95% CI 0.12-0.41) (both p < 0.01), reduced trabecular number by 0.22 per mm (95% CI 0.15-0.28), and increased trabecular separation by 0.07 mm (95% CI 0.05-0.08) (all p < 0.001). Relative to prebreastfeeding, at a median of 2.6 years (range 1 to 4.8) after cessation of breastfeeding, cortical porosity remained 0.58 SD (95% CI 0.48-0.68) higher, matrix mineralization density remained 1.28 SD (95% CI 1.07-1.49) lower, and trabeculae were 1.33 SD (95% CI 1.15-1.50) fewer and 1.06 SD (95% CI 0.91-1.22) more greatly separated (all p < 0.001). All deficits were greater than in controls. The results were similar at distal radius. Bone microstructure may be irreversibly deteriorated after cessation of breastfeeding at appendicular sites. Studies are needed to establish whether this deterioration compromises bone strength and increases fracture risk later in life. © 2016 American Society for Bone and Mineral Research.

Impaired osteogenesis in Menkes disease-derived induced pluripotent stem cells.

IntroductionBone abnormalities, one of the primary manifestations of Menkes disease (MD), include a weakened bone matrix and low mineral density. However, the molecular and cellular mechanisms underlying these bone defects are poorly understood.MethodsWe present in vitro modeling for impaired osteogenesis in MD using human induced pluripotent stem cells (iPSCs) with a mutated ATP7A gene. MD-iPSC lines were generated from two patients harboring different mutations.ResultsThe MD-iPSCs showed a remarkable retardation in CD105 expression with morphological anomalies during development to mesenchymal stem cells (MSCs) compared with wild-type (WT)-iPSCs. Interestingly, although prolonged culture enhanced CD105 expression, mature MD-MSCs presented with low alkaline phosphatase activity, reduced calcium deposition in the extracellular matrix, and downregulated osteoblast-specific genes during osteoblast differentiation in vitro. Knockdown of ATP7A also impaired osteogenesis in WT-MSCs. Lysyl oxidase activity was also decreased in MD-MSCs during osteoblast differentiation.ConclusionsOur findings indicate that ATP7A dysfunction contributes to retardation in MSC development and impairs osteogenesis in MD.Electronic supplementary materialThe online version of this article (doi:10.1186/s13287-015-0147-5) contains supplementary material, which is available to authorized users.

Sclerostin deficiency is linked to altered bone composition.

High bone mass in animals and humans with sclerostin deficiency is associated with increased bone strength, which is not the case for all disorders with high bone mineral density, some of which are even associated with fragility fractures owing to unfavorable bone composition. In the current study we investigated whether alterations in bone composition may contribute to the bone strength characteristics associated with lack of sclerostin. We examined cortical bone of Sost-knockout (KO) mice (n = 9, 16 weeks old) and sclerosteosis patients (young [4 to 14 years], n = 4 and adults [24 and 43 years], n = 2) by quantitative backscattered electron imaging and Raman microspectroscopy and compared it to bone from wild-type mice and healthy subjects, respectively. In Sost-KO mice endocortical bone exhibited altered bone composition, whereas subperiosteal bone was unchanged. When comparing endocortical bone tissue of identical tissue age as defined by sequential dual fluorochrome labeling the average bone matrix mineralization was reduced -1.9% (p < 0.0001, younger tissue age) and -1.5% (p < 0.05, older tissue age), and the relative proteoglycan content was significantly increased. Similarly, bone matrix mineralization density distribution was also shifted toward lower matrix mineralization in surgical samples of compact bone of sclerosteosis patients. This was associated with an increase in mineralization heterogeneity in the young population. In addition, and consistently, the relative proteoglycan content was increased. In conclusion, we observed decreased matrix mineralization and increased relative proteoglycan content in bone subcompartments of Sost-KO mice-a finding that translated into sclerosteosis patients. We hypothesize that the altered bone composition contributes to the increased bone strength of patients with sclerostin deficiency.

Mineral particle size in children with osteogenesis imperfecta type I is not increased independently of specific collagen mutations

Osteogenesis imperfecta (OI) type I represents the mildest form of OI and is usually caused by two classes of autosomal dominant mutations in collagen type I: haploinsufficiency leading to a reduced quantity of structurally normal collagen (quantitative mutation), or sequence abnormalities generating structurally aberrant collagen chains (qualitative mutation). An abnormally high bone matrix mineralization has been observed in all OI cases investigated so far, independently of mutation type. This raises the question whether the increased amount of mineral is due to mineral particles growing to larger sizes or to a higher number of more densely packed particles. For this reason, we revisit the problem by investigating the mineral particle size in cancellous bone from two subsets of the previously analyzed biopsies (patient's age: 2–4.2 and 7.6–11years) comparing OI quantitative mutations (n=5), OI qualitative mutations (n=5) and controls (n=6). We used a combined small-angle X-ray scattering (SAXS) and wide-angle X-ray diffraction (WAXD) setup with a beam diameter of 10μm of synchrotron radiation, which allows the determination of mineral particle characteristics in 10μm thick sections at the same positions where the matrix mineralization density was previously determined. The thickness parameter of mineral particles (T) was obtained from SAXS data and the mineral volume fraction was calculated from the mean calcium content of the bone matrix determined by quantitative back-scattered electron imaging (qBEI). The combination of these two quantities allowed calculating the true particle width (W) of the plate-like mineral crystals.T was larger in the older than in the younger age-group independently of genotype (p<0.004) and was larger in the controls than in each OI group. The qBEI results showed that the mineral volume fraction increased from 32.45wt.% in controls to 36.44wt.% in both OI groups (corresponding to a 12% increase in relative terms). Combining these data, we find that also W was larger in the older than in the younger age-group (p<0.002), but stayed equal or smaller in both OI genotypes (controls: 2.3nm±0.04, OI qualitative: 2.2±0.05; OI quantitative 2.3±0.04, mean±SEM). A linear regression analysis even suggests a slower increase of W in qualitative OI as compared to quantitative OI and controls, where the particle sizes stayed similar at all ages. We thus conclude that the high mineral density in human OI is not due to increased particle size but rather to increased particle packing density. The lack of an observed difference between the two classes of mutations suggests the occurrence of a bone cell defect downstream of the collagen mutation.

Increased matrix mineralization in the immature femoral head following ischemic osteonecrosis

Traditionally, it is believed that structural failure of the ischemic epiphysis as well as changes in radiodensity seen in the early stage of Legg–Calvé–Perthes disease is due to the repair process. However, little is known if matrix properties are altered following ischemic injury of the juvenile femoral head. The purpose of this study was to determine the matrix mineralization density, an important determinant of material quality and strength, of the proximal femoral epiphysis in an experimental animal model of Perthes disease.Ten piglets were surgically induced with femoral head ischemia and euthanized at 4 and 8 weeks following surgery. Contralateral, unoperated femoral heads were used as controls. Bone and calcified cartilage mineralization density distribution parameters were determined using quantitative backscattered electron imaging (qBEI) in the epiphyseal calcified articular cartilage, subchondral bone and central trabecular bone region. Histological as well as radiographic assessment was also performed.In the necrotic calcified epiphyseal cartilage matrix, a significant increase in the mean degree of mineralization (CaMean: +24%, p<0.0001) as well as the homogeneity of mineralization (CaWidth: −21%, p<0.05) and a significantly reduced amount of low mineralized matrix (CaLow: −49%, p<0.0001) were already present at 4 weeks post-ischemia induction. Similar changes, but more moderate, were also seen in the subchondral bone region. In contrast, in the necrotic central trabecular region, significant changes in matrix mineralization were found at 8 weeks (CaMean: +4%, p<0.05; CaWidth: −22%, p<0.05; CaLow: −8%, p<0.05) but not at 4 weeks post-ischemia induction.Our findings indicate that the process of matrix mineralization continues in necrotic calcified articular cartilage and bone following femoral head ischemia, which leads to a higher and more homogenous mineralized tissue matrix altering its intrinsic material properties.This may also explain the increased radiodensity seen in the early stage of Perthes disease prior to the initiation of the repair process.

Estimation of the bone mineral density variation associated with changes in turnover rate

Bone matrix mineral density (BMDn, fraction of maximum) is the mean mineral density of a bone sample comprising moieties of bone of varying ages/mineral densities. A method for calculating BMDn as a function of bone turnover rate is presented. The method is based on a mineralization curve defined by values for mineralization lag time, total mineralization time, and levels of primary and final mineralization. The calculations illustrate that BMDn decreases linearly in direct proportion to increases in bone turnover rate, and that the slope of the line is dependent on the assumptions used to calculate the mineralization curve. BMDn variation is important because it is reflected in whole bone density variation, independent of changes in bone mass, when bone turnover rate is altered.