A theoretical analysis of the relative influences of peak BMD, age-related bone loss and menopause on the development of osteoporosis

Hernandez, Christopher J.; Beaupré, Gary S.; Carter, D. R.

doi:10.1007/s00198-003-1454-8

Cited by 454 publications

(297 citation statements)

References 17 publications

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“…Of potential relevance here, we note that Hernandez 19 suggests the strongest predictor of osteoporosis risk is peak bone mass, estimating a 10% increase would delay the onset of osteoporosis by 10 years.…”

Section: Study Limitationsmentioning

confidence: 82%

Aluminum Exposure From Parenteral Nutrition in Preterm Infants: Bone Health at 15-Year Follow-up

et al. 2009

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OBJECTIVE: Aluminum has known neurotoxicity and may impair short-term bone health. In a randomized trial, we showed reduced neurodevelopmental scores in preterm infants who were previously exposed to aluminum from parenteral nutrition solutions. Here, in the same cohort, we test the hypothesis that neonatal aluminum exposure also adversely affects long-term bone health, as indicated by reduced bone mass. METHODS: Bone area (BA) and bone mineral content (BMC) of lumbar spine, hip, and whole body were measured with dual radiograph absorptiometry in 13- to 15-year-olds who were born preterm and randomly assigned standard or aluminum-depleted parenteral nutrition solutions during the neonatal period. RESULTS: Fifty-nine children (32% of survivors) were followed. Those who were randomly assigned to standard parenteral nutrition solution had lower lumbar spine BMC, apparently explained by a concomitant decrease in bone size. In nonrandomized analyses, children who were exposed to neonatal aluminum intakes above the median (55 μg/kg) had lower hip BMC (by 7.6% [95% confidence interval 0.21–13.8]; P = 0.02), independent of bone (or body) size. CONCLUSIONS: Neonates who are exposed to parenteral aluminum may have reduced lumbar spine and hip bone mass during adolescence, potential risk factors for later osteoporosis and hip fracture. These findings need confirmation in larger, more detailed studies. Nevertheless, given our previous finding of adverse developmental outcome in these individuals and the sizeable number of contemporary infants who undergo intensive neonatal care and are still exposed to aluminum via parenteral feeding solutions, the potential adverse long-term consequences of early aluminum exposure now deserve renewed attention.

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Section: Study Limitationsmentioning

confidence: 82%

Aluminum Exposure From Parenteral Nutrition in Preterm Infants: Bone Health at 15-Year Follow-up

et al. 2009

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“…In part, this may reflect the limitations of DEXA in assessing bone density (by dividing BMC by projected bone area); projected bone area will systematically underestimate the skeletal bone volume of taller individuals; hence, the alternative ratio BMAD has been suggested (8). Recent work using computer models (21) has suggested that a 10% increase in peak BMD is predicted to delay the development of osteoporosis by 13 y, whereas a 10% change in the age at menopause or the rate of nonmenopausal bone loss is predicted to delay osteoporosis by~2 y, reinforcing the importance of peak bone mass in the cause of osteoporosis and fragility fractures. In a different approach, Tabensky et al (22) performed a study of mothers and daughters to demonstrate reduced vertebral volumetric BMD among women who had sustained a vertebral fracture, reflecting reduced accrual of bone during growth in addition to reduced periosteal apposition during aging.…”

Section: Discussionmentioning

confidence: 99%

Birth Weight and Weight at 1 Year Are Independent Determinants of Bone Mass in the Seventh Decade: The Hertfordshire Cohort Study

et al. 2005

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Several studies have shown relationships between growth in early life and adult bone mass; in this article, we evaluate the relative contributions of pre-and postnatal factors to bone mass in the seventh decade. A total of 498 eight men and 468 women who were born in Hertfordshire during the period 1931-1939 and still living there were recruited. Detailed birth records were available. Participants attended a clinic where they completed a detailed health questionnaire, before performance of anthropometric measurements and bone densitometry of the proximal femur and lumbar spine (Hologic QDR 4500). Birth weight was associated with bone mineral content in both men (proximal femur: r ϭ 0.16, p ϭ 0.0003; lumbar spine: r ϭ 0.10, p ϭ 0.03) and women (proximal femur: r ϭ 0.16, p ϭ 0.0008; lumbar spine: r ϭ 0.11, p ϭ 0.03); relationships with bone mineral density were weaker and were significant at the proximal femur in men only (p ϭ 0.03). Relationships between weight at 1 y and bone mineral content were even stronger (proximal femur: men r ϭ 0.22, p Ͻ 0.0001; women r ϭ 0.14, p ϭ 0.002). In men, 18% of the variance in proximal femoral bone area was explained by a model that included birth weight, weight at 1 y, and adult weight, with the relative contributions attributed to each being 2.8, 6.8, and 8.2%, respectively. In women, similar modeling produced figures of 6.7, 4.2, and 3.9% (overall variance of 15% in proximal femoral bone area). Hence, weight at each of these three points in the life course is important in the determination of adult bone mass, with greater contributions of earlier growth to bone size and mineral content than to bone mineral density. Abbreviations BMAD, bone mineral apparent density BMC, bone mineral content BMD, bone mineral density BMI, body mass index DEXA, dual-energy x-ray absorptiometry HRT, hormone replacement therapy Several epidemiologic studies from around the world have shown relationships between growth in early life and adult bone mass. Initial work in Bath (1) and Hertfordshire, UK (2), showed relationships between weight at 1 y and adult bone mineral content (BMC), but more recent studies (3-5) have also found evidence of an association between birth weight and adult bone mass. Furthermore, a Finnish study (6) demonstrated a direct association between low birth length, poor childhood growth, and later risk for hip fracture. Hence, we sought to evaluate the relative contribution of pre-or postnatal growth to the determination of adult bone mass by using a larger birth cohort of men and women who were born in Hertfordshire in the 1930s and still resident there, for whom extensive childhood records, including birth weight and weight at 1 y, were available. METHODSA total of 768 men and 714 women who were aged 60 -75 y completed this study, based around East Hertfordshire. The selection procedure for these individuals was as follows: in brief, with the help of the National Health Service Central Registry at Southport and Hertfordshire Family Health Service Association, we traced men ...

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“…This finding showed that a reduction in the number and size of resorption cavities with antiresorptive drug treatment can result in large reductions in fracture risk with only small increases in bone mass. In another study, Hernandez et al (8) used a computer model of trabecular bone remodeling to study the relative influences of peak BMD, onset time of menopause, and age-related bone loss on the development of osteoporosis. By varying these three parameters by ±10%, the model predicted that the onset of osteoporosis could be delayed longest by increasing peak BMD, which they argued suggests that intervention should focus on this aspect of the disease rather than the others.…”

Section: Background On Conceptual and Mathematical Modeling In Bone Rmentioning

confidence: 99%

In Silico Modeling and Simulation of Bone Biology: A Proposal

Defranoux¹,

Stokes²,

Young³

et al. 2005

Journal of Bone and Mineral Research

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Contemporary, computer-based mathematical modeling techniques make it possible to represent complex biological mechanisms in a manner that permits hypothesis testing in silico. This perspective shows how such approaches might be applied to bone remodeling and therapeutic research.Currently, the dominant conceptual model applied in bone research involves the dynamic balance between the continual build-up and breakdown of bone matrix by two cell types, the osteoblasts and osteoclasts, acting together as a coordinated, remodeling unit. This conceptualization has served extraordinarily well as a focal point for understanding how mutations, chemical mediators, and mechanical force, as well as external influences (e.g., drugs, diet) affect bone structure and function. However, the need remains to better understand and predict the consequences of manipulating any single factor, or combination of factors, within the context of this complex system's multiple interacting pathways. Mathematical models are a natural extension of conceptual models, providing dynamic, quantitative descriptions of the relationships among interacting components. This formalization creates the ability to simulate the natural behavior of a system, as well as its modulation by therapeutic or dietetic interventions. A number of mathematical models have been developed to study complex bone functions, but most include only a limited set of biological components needed to address a few specific questions. However, it is possible to develop larger, multiscale models that capture the dynamic interactions of many biological components and relate them to important physiological or pathological outcomes that allow broader study. Examples of such models include Entelos' PhysioLab platforms. These models simulate the dynamic, quantitative interactions among a biological system's biochemicals, cells, tissues, and organs and how they give rise to key physiologic and pathophysiologic outcomes. We propose that a similar predictive, dynamical, multiscale mathematical model of bone remodeling and metabolism would provide a better understanding of the mechanisms governing these phenomena as well as serve as an in silico platform for testing pharmaceutical and clinical interventions on metabolic bone disease.

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A theoretical analysis of the relative influences of peak BMD, age-related bone loss and menopause on the development of osteoporosis

Cited by 454 publications

References 17 publications

Aluminum Exposure From Parenteral Nutrition in Preterm Infants: Bone Health at 15-Year Follow-up

Aluminum Exposure From Parenteral Nutrition in Preterm Infants: Bone Health at 15-Year Follow-up

Birth Weight and Weight at 1 Year Are Independent Determinants of Bone Mass in the Seventh Decade: The Hertfordshire Cohort Study

In Silico Modeling and Simulation of Bone Biology: A Proposal

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