Age-related Cortical Bone Loss Research Articles

Theoretical concept of cortical to cancellous bone transformation

Microstructures of cortical and cancellous bones are altered continually by load-adaptive remodeling; in addition, their cellular mechanisms are similar despite the remarkably different porosities. The cortico-cancellous transitional zone is a site of vigorous remodeling, and intracortical remodeling cavitates the inner cortex to promote its trabecularization, which is considered the main cause of bone loss because of aging. Therefore, to prevent and treat age-related cortical bone loss effectively, it is indispensable to gain an integrated understanding of the cortical to the cancellous bone transformation via remodeling. We propose a novel theoretical concept to account for the transformation of dense cortical bone to porous cancellous bone. We develop a mathematical model of cortical and cancellous bone remodeling based on the concept that bone porosity is determined by the balance between the load-bearing function of mineralized bone and the material-transporting function of bone marrow. Remodeling simulations using this mathematical model enable the reproduction of the microstructures of cortical and cancellous bones simultaneously. Furthermore, current remodeling simulations have the potential to replicate cortical-to-cancellous bone transformation based on changes in the local balance between bone formation and resorption. We anticipate that the proposed mathematical model of cortical and cancellous bone remodeling will contribute to highlighting the essential features of cortical bone loss due to trabecularization of the cortex and help predict its spatial and temporal behavior during aging.

Osteocyte lacunar properties and cortical microstructure in human iliac crest as a function of age and sex

Osteocytes are suggested to play a central role in bone remodeling. Evaluation of iliac crest biopsies is a standard procedure for evaluating bone conditions in the clinical setting. Despite the widespread use of such biopsies, little is known about the population of osteocytes in the iliac crest from normal individuals. Contradicting results have been reported on osteocyte lacunar properties in human bone. Hence, a solid understanding of the osteocyte population in healthy bone and the effect of age and sex is needed as good reference data are lacking. Furthermore, the role of cortical bone in bone quality has recently been suggested to be more important than previously realized. Therefore, the present study assesses osteocyte lacunar properties and cortical microstructure of the iliac crest as a function of age and sex. A total of 88 iliac crest bone samples from healthy individuals (46 women, aged 18.5–96.4years and 42 men, aged 22.6–94.6years) with an even age-distribution were examined using synchrotron radiation μCT and in house μCT, with >5×106 osteocyte lacunae measured and analyzed. The study revealed that osteocyte lacunar volumes were unaffected by both age and sex. Osteocyte lacunar density did not differ between women and men, and only showed a significant decrease with age when pooling data from both sexes. Cortical porosity and Haversian canal density increased while cortical thickness decreased with age, with cortical thinning dominating the age-related cortical bone loss. None of the cortical microstructural parameters showed any sex dependency. Only weak links between osteocyte lacunar properties and cortical microstructural properties in iliac crest bone were found. Interestingly, the Haversian canal diameters were significantly but weakly negatively correlated with osteocyte lacunar volumes.

The Periosteal Bone Surface is Less Mechano-Responsive than the Endocortical.

Dynamic processes modify bone micro-structure to adapt to external loading and avoid mechanical failure. Age-related cortical bone loss is thought to occur because of increased endocortical resorption and reduced periosteal formation. Differences in the (re)modeling response to loading on both surfaces, however, are poorly understood. Combining in-vivo tibial loading, in-vivo micro-tomography and finite element analysis, remodeling in C57Bl/6J mice of three ages (10, 26, 78 week old) was analyzed to identify differences in mechano-responsiveness and its age-related change on the two cortical surfaces. Mechanical stimulation enhanced endocortical and periosteal formation and reduced endocortical resorption; a reduction in periosteal resorption was hardly possible since it was low, even without additional loading. Endocortically a greater mechano-responsiveness was identified, evident by a larger bone-forming surface and enhanced thickness of formed bone packets, which was not detected periosteally. Endocortical mechano-responsiveness was better conserved with age, since here adaptive response declined continuously with aging, whereas periosteally the main decay in formation response occurred already before adulthood. Higher endocortical mechano-responsiveness is not due to higher endocortical strains. Although it is clear structural adaptation varies between different bones in the skeleton, this study demonstrates that adaptation varies even at different sites within the same bone.

Normative Data for Digital X-Ray Radiogrammetry From a Female and Male German Cohort

This study presents German reference data for digital X-ray radiogrammetry (DXR) differentiated by males as well as females, and quantifies for gender-specific and age-related differences including all DXR parameters. This study also documents the effects of different X-ray settings (e.g., radiographs of the wrist or the hand) on DXR measurements. There were 2085 patients who were prospectively enrolled (954 females and 1131 males) from a data pool of 11,915 patients with radiographs of the nondominant hand or wrist. All patients underwent measurements of bone mineral density (BMD), cortical thickness, bone width, and the metacarpal index (MCI) using DXR technology. These data showed a continuous age-related increase of the DXR parameters to the point of peak bone mass, then a continuous decline beyond the peak bone mass with accentuated age-related cortical bone loss in women. Peak bone mass is reached at approximately 30-34 yr for women and 45-49 yr for men. In addition, men had a significantly higher DXR BMD (mean: +12.8%) compared with woman in all age groups. Regarding the impact of various X-ray settings (e.g., X-ray(wrist) vs. X-ray(hand)), no significant difference was observed between both groups, men as well as women. The development of digital imaging technology has enabled more precise measurements of several radio-geometric features. The present study estimated normative reference values for DXR in German Caucasian women and men. Based on this reference data, a valid and reliable quantification of disease-related demineralization based on measurements of DXR BMD and MCI is now available for the Caucasian ethnic group.

Metacarpal radiogrammetry: a useful indicator of bone loss throughout the skeleton?

Metacarpal radiogrammetry has received increasing interest in recent studies of archaeological human bone in facilitating the identification of age-related cortical bone loss and osteoporosis risk in the past. The technique is relatively simple and non-destructive, and existing comparative clinical data is an advantage in its application to archaeological samples. In order for metacarpal radiogrammetry to be useful in identifying individuals that could have been at risk of fracture in the past, cortical bone loss as measured at the second metacarpal is assumed to be reflective of bone loss occurring throughout the skeleton and across the metabolically different cortical and trabecular bone. Archaeological studies have frequently relied on literature reviews of clinical data to justify the technique as valid and useful. However, the present study has examined whether cortical bone loss measured in the second metacarpal is similar to bone loss measured at specific skeletal sites that are more frequently affected by osteoporosis-related fracture. Skeletons from two post-medieval collections from London, UK, Redcross Way and Farringdon Street (lower burial ground of St. Bride's Church) were studied. The results of the present study demonstrate that the second metacarpal is useful in identifying age-related bone loss at sites that are predilected to osteoporotic fracture, most notably the distal radius, which is prone to Colles' fractures. Metacarpal radiogrammetry also correlates well with bone loss in skeletal sites that are primarily composed of trabecular bone, including the fourth lumbar vertebra (a site of compression fractures) and the iliac crest (the location for clinical biopsies). The present study also confirms previous findings of significant differences between the pattern of cortical bone loss between the metacarpal and the femur. The poor relationship between these two areas is most likely attributable to mechanical loading.

Age-related changes in cortical bone in men: metacarpal bone mass measurement study

Metacarpal cortical bone mass was measured in 507 healthy Japanese men aged 40–95 years, using a microdensitometer to determine age-related changes in cortical bone in these middle-aged and elderly men. Total bone mass showed a significant negative correlation with age (r = −0.281; P < 0.0001). While bone width showed no significant correlation with age, bone marrow width showed a significant positive correlation (r = 0.210; P < 0.0001), and cortical bone width and cortical bone density showed a significant negative correlation with age (r = −0.265; P < 0.0001; r = −0.268; P < 0.0001, respectively). On the other hand, cortical bone width and cortical bone density showed a significant positive correlation with total bone mass (r = 0.814; P < 0.0001; r = 0.474, P < 0.0001, respectively). These findings suggest that cortical bone mass decreases significantly with aging in middle-aged and elderly men, perhaps as a result of two factors — decreased cortical bone width, ie, cortical bone thinning due to bone loss at the endosteal side of the cortex, and decreased cortical bone density due to progression of intracortical porosity. Cortical bone thinning may influence age-related cortical bone loss more than decreasing cortical bone density.

Age-related decline of bone mass and intestinal calcium absorption in normal males.

Although about 25% of all hip fractures occur in men, little is known about the pattern of their age-related bone loss and its main determinants. The aim of this cross-sectional study was to evaluate the age-related changes of intestinal calcium absorption, bone mass, and bone turnover in normal men. In 70 normal males (age 17-91 years), we measured spinal and forearm bone density (FBD) (by DXA), fractional intestinal calcium absorption (by oral test), serum immunoreactive parathyroid hormone (PTH), dietary calcium intake (diet records), biochemical markers of bone turnover (serum alkaline phosphatase (ALP), osteocalcin, urine calcium, creatinine, and hydroxyproline), and 1,25(OH)2D3 serum levels. Vertebral bone density (VBD) showed a modest decline before age 50 and a greater decline after age 50, whereas FBD presented a significant decrease with advancing age starting at age 40, suggesting a predominant age-related cortical bone loss. Intestinal calcium absorption (47CaFA) and serum 1,25(OH)2D3 also presented an age-related decline similar to FBD. Simple correlation analysis revealed that age was significantly related to 47CaFA (r = 0.60), calcium intake (r = 0.32), VBD and FBD (r = 0.79 and 0.63, respectively), serum 1,25(OH)2D3 (r = 0.69), and serum iPTH (r = 0.72). No significant correlation was found between age and biochemical markers of bone remodeling. Partial correlation and stepwise variable selection analyses, using 47CaFA and bone mass as dependent variables, showed that in normal males, serum 1,25(OH)2D3 and dietary calcium intake were the main contributors (64%) to 47CaFA variability, whereas only age accounted for 63% of VBD and age and dietary calcium accounted for 45% of FBD variability. These results indicate that bone loss in men accelerates after age 50 years and that among other factors, intestinal calcium malabsorption and 1,25(OH)2D3 serum levels play a role.

A Structural Approach to Renal Bone Disease

A Structural Approach to Renal Bone Disease

Age-related changes in cortical bone in women: Metacarpal bone mass measurement study

The mechanism of age-related cortical bone loss was investigated in 229 Japanese women, 41–94 years of age, by metacarpal bone mass measurement. While no significant correlation was found between bone width and age, a significant increase in bone marrow width, and significant decreases in cortical bone density and total bone mass were observed in association with aging (P < 0.0001). There was a significant negative correlation between total bone mass and bone marrow width (r = −0.239; P < 0.0005), and significant positive correlations between both total bone mass and cortical bone density (r = 0.539; P < 0.0001) and cortical bone width (r = 0.839; P < 0.0001). The findings suggested that age-related cortical bone loss in middle-aged and elderly women resulted from two different factors; a decrease in cortical bone density caused by progression of intracortical porosity, and a decrease in cortical bone width as a result of bone loss on the endosteal surface. The latter had a greater influence on an age-related cortical bone loss than the former.

Age-related cortical bone loss at the metacarpal.

In order to evaluate in vivo the entity of endosteal and periosteal changes with age in the two sexes, and their relative contribution to age-related cortical bone loss, we undertook a cross-sectional study on a population of normal Caucasian subjects. The group included 189 women and 107 men who were studied by photodensitometry and radiogrammetry of the second metacarpal bone, derived from the same standard hand X-ray. Of the subjects, 134 were 65 years of age or older (75 women and 59 men). Metacarpal bone mineral density (BMD) correlated with age in both sexes, with an annual bone loss rate of 0.5% in women and 0.15% in men. In the over 65 group, correlation was significant only in women, who underwent an acceleration in the rate of bone loss (1% per year). Marrow cavity width (M), cortical index at the second metacarpal shaft (MI) and external width (W) all correlated with age in both sexes, although generally better in the female than in the male sex. M almost doubled from the fourth to the ninth decade in women and increased 50% in men. In the same age interval, MI showed an annual decrease of 0.49% in females and 0.33% in males. In the over 65 group, cortical thinning rate was significant in women (0.39% per annum) but not in men (0.14% per annum), whereas correlation of W was not significant in either sex. Finally, MI correlated with BMD in the whole study population and in the over 65, with a female prevalence in correlation strength maintained throughout life. The following conclusions can be derived for metacarpal aging: (1) an acceleration in cortical bone loss occurs in females after age 65; (2) age-related growth in periosteal diameter, although significant in the whole population, is negligible in the elderly of both sexes; (3) age-related cortical bone loss is generally more dependent on cortical thinning in women than in men.