Peak bone mass and osteoporosis prevention.
It is important to promote bone health at all ages; Childhood and young adulthood are the bone building years; As children grow, their bone mass increases until. Description of the development the bones take until their peak mass. 5 Explain what peak bone mass is and its relationship to osteoporosis 1 point from A&P 1 What are some examples of steroid prescription medications?.
The gender difference in bone mass is expressed during puberty. This difference appears to be due mainly to a more prolonged bone maturation period in males than in females, with a larger resulting increase in bone size and cortical thickness. Puberty affects bone size much more than it does vBMD. There is no significant sex difference in volumetric trabecular density at the end of pubertal maturation. The increment in bone mass gain is less marked in long bone diaphyses.
It certainly represents an important macro-architectural determinant of the difference in the incidence of vertebral fragility fractures observed between female and male subjects in later life. Within each gender, this structural property also plays an important role in vertebral fracture risk. In postmenopausal women, a smaller cross-sectional area of vertebral bodies was measured in those with than without vertebral fractures despite the fact that the two groups displayed equally low trabecular vBMD as determined by spinal QCT.
There is an asynchrony between the gain in standing height and the growth of bone mineral mass during pubertal maturation. It is possible that some of these fractures may also be determined by tracking, from infancy to the end of skeletal maturation, along a relatively low bone mass percentile Z-score.
In adolescent females, gain in bone mass declines rapidly after menarche; no further statistical gains are observed 2 years later at least in sites such as the lumbar spine or femoral neck. As described above the change in vBMD during growth is very modest as compared to the increment in bone size.
Furthermore the increased vBMD as measured by QCT has been detected in vertebral cancellous bone but not in appendicular cortical tissue. This is in keeping with numerous observations indicating that at most skeletal sites, total bone mineral mass does not significantly increase from the third to the fifth decade.
Nevertheless, a few cross-sectional studies suggest that bone mass acquisition may still be substantial during the third and fourth decades. In any case, the balance of published data does not sustain the concept that bone mass at any skeletal site, in either gender and in any ethnic geographic population group, continues to accumulate through the fourth decade. However, several observations are not consistent with such an increased range in aBMD values in relation to age.
In untreated post-menopausal women, the standard deviation SD of bone mineral mass measured at both the proximal and distal radius was not greater in women aged 70 to 75 compared to 55 to 59 years. Thus, at both the lumbar spine and femoral neck, the range of aBMD values was no wider in women aged 70 to 90 years old than in women aged 20 to 30 years.
The notion of 'tracking' has two important implications. First, the prediction of fracture risk based on one single measurement of femoral neck aBMD remains reliable in the long term.
From these two implications, it can be inferred that the bone mass acquired at the end of the growth period appears to be more important than the bone loss occuring during adult life.
Load was determined by upper body weight, height and the muscle moment arm, and bone strength estimated from the bone cross-sectional area CSA and vBMD.
From young to older adulthood, this index increased more in women Chinese and Caucasian than men of the same ethnicity. Similar conclusion was reached concerning the construction of the femoral neck.
Determinants of peak bone mass and strength Several interconnected factors influence bone mass accumulation during growth. These physiological determinants classically include heredity, vitamin D and bonetropic nutrients calcium, proteinsendocrine factors sex steroids, IGF-I, 1.
Quantitatively, the most prominent determinant appears to be genetically related. Heredity Mass Parent-offspring comparison studies reveal a significant relationship in the risk of osteoporosis within families, with apparent transmission from either mothers or fathers to their children. This "genetic effect" appears to be greater in skeletal sites such as the lumbar spine compared to the femoral neck.
Two main approaches have dominated the search for genetic factors that would influence bone acquisition and thereby modify the susceptibility to osteoporosis in later life.
One approach is to search by genome-wide screening for loci flanked by DNA micro-satellite markers that would co-segregate with the phenotype of interest in a population of related individuals.
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The pedigrees investigated to date consist mainly of families with a member at either extreme of the skeletal phenotype spectrum, particularly those exhibiting either very high or very low bone mineral mass or areal density.
The second most frequently used approach is to search for an association between allelic variants or polymorphisms of genes coding for products that are implicated in bone acquisition or loss. Numerous polymorphisms of "candidate" genes have been found to be associated with aBMD, so far the most convenient measurable surrogate of bone mass and strength. The genes studied code for molecules implicated in bone function and structure such as circulating endocrine factors, hormone receptors, local regulators of bone modeling and remodeling or matrix molecules.
None of these genes appears to account for more than a few percent of PBM variance. Identifying the implicated genes interacting with bone-specific nutrients and the response to mechanical loading represents a formidable, but hopefully not intractable, challenge. As specified above, the development of bone mineral mass during the entire growth period, including during pubertal maturation, is essentially due to an increase in bone size, with very mild changes in the amount of mineralized tissue within the bone envelope.
In adulthood, patients affected by the androgen insensitivity syndrome, with XY genotype and a marked female phenotype are taller than the average standing height of the corresponding female population. They exert biphasic effects by accelerating bone growth at the beginning of puberty whereas in both genders, estrogens are key determinants for the closing of growth plates. In female subjects, bone mineral mass increases more by endosteal than periosteal accrual. To a large extent, they explain the greater risk of osteoporotic fractures occurring in adult women than men.
The increased bone mineral apposition at the level of the endosteal surface during puberty in female subjects may teleologically represent a biological adaptation allowing the rapid mobilization of bone mineral in response to the increased needs during pregnancy and lactation. A later age at menarche was found to be associated with lower aBMD in the spine and proximal femur35,36 and higher risk of vertebral37 and hip fracture38 in adulthood.
Indirect evidence from a retrospective epidemiological survey suggests that this association is likely to be related to the influence of pubertal timing on PBM attainment. In premenopausal women, early compared to late menarche, is associated with higher aBMD. Although this intuitive explanation appears to be quite reasonable, there is no unequivocal evidence demonstrating that sex hormone exposure is the essential causal factor accounting for the association between pubertal timing and the risk of osteoporosis.
The growth hormone-insulin-like growth factor-1 system From birth to the end of adolescence, the GH-IGF-1 system is essential for harmonious skeleton development. During puberty, the plasma level of IGF-1 rises transiently according to a pattern that is similar to the curve of the gain in bone mass and size.
This factor exerts a direct action on both growth plate chondrocytes and osteogenic cells responsible for building both cortical and trabecular bone tissue constituents.
This activity is also expressed by parallel changes in the circulating biochemical markers of bone formation, osteocalcin and alkaline phosphatase. In addition, IGF-1 exerts an important impact on renal endocrine and transport functions that are essential for bone mineral economy.
IGF-1 receptors are localized in the renal tubular cells. They are connected to both the production machinery of the hormonal form of vitamin D, namely 1,25 OH 2D and to the transport system of inorganic phosphate Pi localized in the luminal membrane of the tubular cells.
Coupled to the stimulation of the tubular capacity to reabsorb Pi, the extra cellular Ca-Pi product is increased by IGF-1, which, through this dual renal action, favors the mineralization of the bone matrix. Furthermore, at the bone level, IGF-1 still directly enhances the osteoblastic formation of the extra cellular matrix. In growth plate chondrocytes as well as in their plasma membrane derived extra cellular matrix vesicles are equipped by a phosphate transport system that plays a key role in the process of primary calcification and thereby in bone development.
This Pi transport system is also present in other osteogenic cells43 and interestingly, is regulated by IGF The hepatic production of IGF-1, which is the main source of its circulating level, is influenced not only by GH, but also by other factors, particularly by amino acids from dietary proteins figure 2.
The modalities of this interaction have still to be delineated in humans. From animal studies, relatively low concentrations of estrogens would appear to stimulate the hepatic production of IGF-1, whereas large concentrations apparently exert an inhibitory effect. Mechanical forces impinge on the skeleton by enhancing osteoblastic bone formation, while inhibiting osteoclastic bone resorption.
Some appear to be produced by the osteocytes. The density, distribution and extensive communication network of osteocytes make them particularly well structured to function as detectors of mechanical strain by sensing fluid movement within the bone canaliculi.
They can direct the formation of new bone by activating lining cells to differentiate in preosteoblasts. Sclerostin can bind and antagonize LRP5, a Wnt co-receptor that is required for bone formation in response to mechanical load.
Mechanical loading can induce a marked reduction of sclerostin in both osteocytes and in the canaliculi network. The mechanosensation and transduction in osteocytes still involve other factors including nitric oxide NOprostaglandins and ATP. Age and optimal response to loading. Growing bones are usually more responsive to mechanical loading than adult bones.
Physical activity increases bone mineral mass accumulation in both children and adolescents. However, the impact appears to be stronger before than during or after the period of pubertal maturation. The greater gain in aBMD or BMC in young athletes compared with less active controls is preferentially localized in weight bearing bones, such as the proximal femur.
Studies in adult elite athletes strongly indicate that increased bone mass gains resulting from intense physical activity during childhood and adolescence are maintained after training attenuates or even completely ceases. Exercise during growth and fracture prevention in adulthood.
The question whether the increased PBM induced by physical exercise will be maintained into old age and confer a reduction in fracture rate remains uncertain. A cross-sectional study of retired Australian elite soccer players suggested that this might not be the case. In the perspective of public health programs aimed at increasing bone mineral mass gain in children and adolescents, it is obvious that only physical exercise of moderate intensity, duration and frequency, but which would still be effective, can be taken into consideration.
In children, prepubertal individuals or those at an early stage of sexual maturation, several interventions implemented within the school curriculum indicate that moderate exercise can impact positively on bone development.
Nevertheless, it remains uncertain to what extent the greater aBMD gain in response to moderate and readily accessible weight-bearing exercise is associated with a commensurate increase in bone strength. The magnitude of benefit in terms of bone strength will depend upon the nature of the structural change.
An effect consisting primarily of an increased periosteal apposition and consecutive diameter will confer greater mechanical resistance than a response limited to the endosteal apposition rate leading essentially to a reduction in the endocortical diameter. Recent studies suggest site-specific differences in how the pre-pubertal skeleton develops in response to repetitive loading.
Role of energy intake and muscle mass development. In healthy subjects, the energy intake is adjusted to increased physical activity. Hence it is difficult to ascribe the additional gain in bone mass to mechanical loading alone.
Indeed, nutrients such as calcium and proteins, that are usually consumed in various amounts in relation to physical activity, could substantially contribute to the positive effect on bone mass acquisition. The independent mechanical contribution can be measured by the differential effect observed according to the skeletal sites solicited. However, the best evidence of the distinct effect of mechanical loading from concomitant increase in nutritional intakes is provided by studies on the use of rackets, as determined by measuring the difference between loaded and unloaded arms.
It has been suggested that the exercise-induced gain in bone mass, size and strength essentially results from an adaptation secondary to the increase in muscle mass and strength. Impaired bone mass acquisition can occur when intensive physical activity leads to hypogonadism and low body mass. Intake of energy, protein and calcium may be inadequate as athletes go on diets to maintain an idealized physique for their sport.
Intensive training during childhood may contribute to a later onset and completion of puberty. Hypogonadism, as expressed by the occurrence of oligomenorrhea or amenorrhea, can lead to bone loss in females who begin training intensively after menarche. The differential impact of calcium The extent to which variations in the intake of certain nutrients by healthy, apparently well-nourished, children and adolescents affect bone mass accumulation, particularly at sites susceptible to osteoporotic fractures, has received increasing attention over the last 15 years.
Most studies have focused on the intake of calcium. However, other nutrients such as proteins, which are not discussed in this review, should also be considered. In most regions of the world, the supply of calcium is sufficient to avoid the occurrence of clinically manifest bone disorders during growth. Nevertheless, by securing adequate calcium intake, provided the skin and food supply of vitamin D is adequate, it is expected that bone mass gain can be increased during infancy, childhood and adolescence and thereby optimal PBM can be achieved.
The prevention of adult osteoporotic fractures is the main reason for this widespread preoccupation. International and national agencies have adopted recommendations for calcium intake from infancy to the last decades of life.
Decisions from these recommending bodies can be based on either calcium balance, allowing estimations to be made regarding maximal retention, or on a factorial method that calculates from available data on calcium accretion and endogenous losses modified by fractional absorption.
Observational and interventional studies are also taken into consideration. The recommendations vary widely among regional agencies56 table I. Thus, for children aged years, the recommended daily calcium intakes are set at,and up to mg, in the United Kingdom, the Nordic European countries, France and the United States of America, respectively.
Variability in calcium intake recommendations can be explained partly by the discrepant results obtained in observational and interventional studies. Retrospective epidemiological data obtained in women aged years, indicated that milk consumption during childhood and adolescence can be positively correlated to bone mineral mass. Several calcium intervention studies have been carried out in children and adolescents. Nevertheless, the response appears to vary markedly according to several factors including the skeletal sites examined, the stage of pubertal maturation, the basal nutritional conditions, i.
The benefit of supplemental calcium was usually greater in the appendicular that in the axial skeleton. In agreement with our longitudinal observation in healthy subjects aged 8 to 19 years figure 6the skeleton appears to be more responsive to calcium supplementation before the onset of pubertal maturation than during the peripubertal period. Two co-twin studies strongly suggest that increasing calcium intake after the onset of pubertal maturation above a daily spontaneous intake of about mg does not exert a significant positive effect on bone mineral mass acquisition.
This contrasts to the widespread intuitive belief that the period of pubertal maturation with its acceleration of bone mineral mass accrual would be the most attractive time for enhancing calcium intake well above the prepubertal requirements. As described above efficient adaptive mechanisms secure an adequate bone mineral economy in response to the increased demand of the peripubertal growth spurt. As intuitively expected, the benefit observed at the end of intervention is particularly substantial in children with a relatively low calcium intake.
In contrast, the additional gain was minimal in those girls with a relatively high calcium intake. According to the "programming" concept, environmental stimuli during critical periods of early development can provoke long-lasting modifications in structure and function of various biological systems.
The possibility that physical activity could modulate the bone response to dietary calcium supplementation during growth has been considered in infants, children and adolescents. Overall, the results suggest an interaction: At moderately low calcium intake, the effect may not be positive. Thus, in a longitudinal study in infants months of age, i. In young children aged years, either calcium supplement or gross motor activity increased bone mass accrual as compared to either placebo or fine motor activity.
This regional specificity suggests that the effect of physical activity alone or combined with relatively high calcium supply is not merely due to an indirect influence on the energy intake, which in turn would positively affect bone mass acquisition. It has not been established whether the type of calcium salt used to supplement diets may modulate the nature of the bone response. The observation that calcium supplementation can increase bone size, at least transiently, has been observed using either milk extracted calcium-phosphate as well as calcium carbonate salt.
Another uncertainty is the question of whether gains observed by the end of the intervention are maintained or lost after discontinuation of calcium supplementation. A clear answer to this question requires long term follow up, since sustained gain even on bone mass and size may be transient, possibly resulting from some indirect influence of calcium supplementation on the tempo of pubertal and thereby bone maturation.
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The observational and interventional studies discussed above illustrate the numerous factors that can modulate the bone response to calcium intake. This foregoing analysis may, at least in part, explain the difficulty to reach a scientifically based worldwide consensus on dietary allowance recommendation for children and adolescents.
Nevertheless, taking into account both the results of all studies as well as our knowledge on the physiology of calcium and bone metabolism, particularly on the adaptive mechanisms operating during the peripubertal period,61 it appears reasonable and safe to recommend food intake that would provide about mg of calcium per day from prepuberty to the end of adolescence.
Assessment of fracture risk and its application to screening for postmenopausal osteoporosis. Report of a WHO study group. Briot K, Roux C. Best Pract Res Clin Rheumatol ;19 6: Specker BL, Schoenau E. Quantitative bone analysis in children: J Pediatr ; 6: Osteoporos Int ;4 Suppl 1: Familial resemblance for bone mineral mass is expressed before puberty. J Clin Endocrinol Metab ;83 2: Differential effect of race on the axial and appendicular skeletons of children.
J Clin Endocrinol Metab ;83 5: Pathogenesis of bone fragility in women and men. Longitudinal monitoring of bone mass accumulation in healthy adolescents: Evidence for a marked reduction after 16 years of age at the levels of lumbar spine and femoral neck in female subjects. J Clin Endocrinol Metab ;75 4: Relative contribution of vertebral body and posterior arch in female and male lumbar spine peak bone mass.
Osteoporos Int ;4 5: How is osteoporosis related to menopause? There is a direct relationship between the lack of estrogen after menopause and the development of osteoporosis. After menopause, bone resorption breakdown overtakes the building of new bone. Early menopause before age 45 and any long phases in which the woman has low hormone levels and no or infrequent menstrual periods can cause loss of bone mass. What are the symptoms of osteoporosis?
Osteoporosis is often called the "silent disease" because bone loss occurs without symptoms. People may not know that they have osteoporosis until their bones become so weak that a sudden strain, bump, or fall causes a fracture or a vertebra to collapse. Collapsed vertebrae may be first noticed when the person suffers severe back pain, loss of height, or spinal deformities such as stooped posture.
Important risk factors for osteoporosis include: After maximum bone density and strength is reached generally around age 30bone mass begins to naturally drop with age.
Women over the age of 50 have the greatest risk of developing osteoporosis. In fact, women are four times more likely than men to develop osteoporosis. Research has shown that Caucasian and Asian women are more likely to develop osteoporosis. Additionally, hip fractures are twice as likely to occur in Caucasian women as in black women. However, women of color are more likely to die after a hip fracture Bone structure and body weight.
Peak bone mass and osteoporosis prevention.
Petite and thin women have a greater risk of developing osteoporosis because they have less bone to lose than women with more body weight and larger frames. Similarly, small-boned, thin men are at greater risk than men with larger frames and more body weight Family history.
Heredity is one of the most important risk factors for osteoporosis. If your parents or grandparents have had any signs of osteoporosis, such as a fractured hip after a minor fall, you may be at greater risk of developing the disease How can I know if I have osteoporosis? A painless and accurate test can provide information about your bone health before problems begin.
Bone mineral density BMD tests, or bone measurements, are X-rays that use very small amounts of radiation to determine bone density. In addition to measuring bone health, the test can determine how severe any osteoporosis is. Please note that women with no other risk factors whose BMD T-scores are below Women with BMD T-scores below Your doctor will talk to you about your own risks for fracture to determine if you need medication.
Who should have a bone mineral density test? All post-menopausal women who suffer a fracture that is suspicious for osteoporosis. All post-menopausal women under age 65 who have one or more additional risk factors. All post-menopausal women age 65 and over, regardless of additional risk factors. How is osteoporosis treated? Weight-bearing exercises which make your muscles work against gravity Calcium and vitamin D supplements Prescription medications such as: Hormone therapy HT is believed to be useful in preventing or decreasing the increased rate of bone loss that leads to osteoporosis.
Hormone therapy is generally recommended for postmenopausal women who have: An early menopause A low bone mass, as measured by a bone density test and menopausal symptoms Several other risk factors for osteoporosis, such as: Breast cancer Blood clots High blood pressure in some women If you are using HT to prevent osteoporosis, be sure to talk to your doctor so that you can weigh the benefits of HT against your personal risk for heart attack, stroke, blood clots, and breast cancer.
If needed, your doctor can prescribe different treatments to prevent osteoporosis and fractures. Estrogen therapy alone has been shown to have less risk than combination hormone therapy. Your doctor can provide you more information about how your health history fits in with the risks and benefits of hormone therapy. Are there alternatives to hormone therapy for osteoporosis?
For those women who cannot take hormone therapy for health reasons, or who choose not to for personal reasons, there are alternatives: Fosamax, Actonel, Atelvia, Boniva. These drugs belong to a class of drugs called bisphosphonates, which prevent bone breakdown. They are used to prevent and treat osteoporosis. They have been shown to slow bone loss, increase bone density, and reduce the risk of spine and non-spine fractures. They may be considered in postmenopausal women who are at risk of developing osteoporosis who wish to maintain bone mass and to reduce the risk of fracture.
Boniva is also available in intravenous IV, by needle form, given every 3 months by a nurse. Atelvia is a weekly delayed-release formulation which eliminates the need to take the medication on an empty stomach Reclast.
This is an IV bisphosphonate therapy that can be given once a year to treat osteoporosis, or once every other year for prevention in patients with osteopenia reduced bone mass.
Reclast is a good alternative for patients who have problems taking bisphosphonates by mouth.
It reduces bone loss, and reduces the risk of both spine and hip fractures Fortical, Miacalcin. These drugs are made up of a naturally occurring hormone called calcitonin. In women who are at least five years past menopause and have osteoporosis, these drugs slow bone loss and increase density in the spinal bone. Women report that they also ease the pain of bone fractures.
However, these drugs are rarely used anymore because there are very few studies about how effective they are. Also, it has been reported to the FDA that there may be a link between these drugs and cancer Evista. It is approved for prevention and treatment of osteoporosis and can prevent bone loss at the spine, hip, and other areas of the body. Studies have shown that Evista can decrease the rate of vertebral back fractures by 30 to 50 percent.
This medication has been shown to reduce breast cancer risk. It has the same risk of blood clots as hormone therapy Prolia. This is an antibody that helps stop the development of bone-removing cells before they cause bone loss. Patients taking Prolia might be at greater risk for infection How can I prevent osteoporosis?