Initial Bone Mass Research Articles

Factors affecting bone mineral density in children and adolescents with secondary osteoporosis.

This study aimed to investigate the clinical factors associated with bone mineral density (BMD) among children and adolescents with osteoporosis secondary to treatment for underlying clinical conditions. We retrospectively reviewed the medical records of patients aged 10-18 years and evaluated them for lumbar spine BMD (LSBMD) after treatment for underlying diseases, including hemato-oncologic, rheumatologic system, and inflammator y bowel diseases. LSBMD measured by dual-energy x-ray absorptiometry (DXA) performed from March 2019 to March 2021 was evaluated. We analyzed 117 patients who underwent initial DXA after treatment for underlying diseases. Subjects in this study had multiple underlying diseases: hemato-oncologic (78.6%), rheumatologic (11.1%), and inflammatory bowel diseases (10.3%). There was no significant association between the z-score and bone metabolic markers (P>0.05). However, higher cumulative glucocorticoid (GC) dose significantly reduced LSBMD z-score (P=0.029). Moreover, the association between cumulative dose of GC and initial z-score of LSBMD was significant in logarithmic regression analysis (P=0.003, R2=0.149). GC accumulation was a significant risk factor for vertebral fracture when the initial BMD was evaluated after treatment (P=0.043). Bone metabolic markers did not significantly influence the risk of vertebral fracture. Initial bone mass density of the lumbar spine evaluated after long-term GC use for underlying diseases is a predictor of further vertebral fractures.

Effects of lipid extraction and ultrafiltration on stable carbon and nitrogen isotopic compositions of fish bone collagen.

Fish bone collagen isotopic measurements are increasingly important in palaeodietary and paleoenvironmental studies yet differences in the chemical and physical properties of fish relative to other vertebrate bones are rarely considered. Lipid content in fish bone, which can exceed 50%, may underlie the poor collagen integrity criteria typically observed in archaeological studies. We compare stable carbon and nitrogen isotopic and elemental compositions of bone collagen prepared using four different methods from a wide range of modern fish species to: (1) assess the extent to which lipid content influences bone collagen δ(13) C and δ(15) N values, and (2) evaluate the relative efficacy of chemical (2:1 chloroform/methanol) and physical (30 kDa ultrafilters) methods for removing lipids from bones. Lower δ(13) C values were observed when the lipid content exceeded 5% of the initial bone mass. The lipid content did not influence the δ(15) N values. 30 kDa ultrafiltration, a common pretreatment for purifying archaeological collagen, removed fewer lipids and was associated with reduced collagen yields (37% loss) as well as altered amino acid compositions. In contrast, collagen prepared using a 2:1 chloroform/methanol lipid extraction step resulted in significantly improved collagen yields, elemental compositions, and isotopic measurements relative to a control treatment. The chemical lipid extraction method (2:1 chloroform/methanol) performed significantly better than the physical lipid extraction method (30 kDa ultrafilters). Given the high quantities of lipids in fish bones we recommend the inclusion of a chemical lipid extraction step when isolating collagen from modern and archaeological fish bones. Copyright © 2016 John Wiley & Sons, Ltd.

Subchondral bone sclerosis and cancellous bone loss following OA induction depend on the underlying bone phenotype

ObjectivesOsteoarthritis (OA) is increasingly considered a disease of the whole joint, yet the interplay between the articular cartilage and the subchondral bone remains obscure. We here set out to investigate the impact of bone mass on the progression of surgically induced knee OA in the mouse. MethodsOA was induced in the right knees of female C57BL/6 (low bone mass) and STR/ort (high bone mass) mice via anterior cruciate ligament transection and destabilization of the medial meniscus. At 36 weeks of age, left and right knee joints were histologically compared for cartilage degeneration and via microCT analysis for subchondral bone plate thickness. In addition, femora were analyzed for bone mass at diaphysis and distal meta- and epiphysis. ResultsThe severity of cartilage deterioration did not differ under high and low bone mass conditions. However, the extent of bone sclerosis differed and was proportional to the baseline subchondral bone plate thickness. Moreover, the cancellous bone loss following OA progression was inversely related to the bone mass: high bone mass restricted the loss to the epiphysis, whereas low bone mass allowed for a more widespread loss extending into the metaphysis. ConclusionsOur results suggest that cartilage degeneration is independent of the underlying bone mass. In contrast, subchondral bone remodeling associated with OA progression seem to correlate with the initial bone mass and suggest an enhanced crosstalk between the deteriorating cartilage and the subchondral bone under low bone mass conditions.

Nutrition in bone growth and development

The greatest increase in bone density was observed around ages 10-14 years in girls and thereafter peak bone mass was attained. Maximizing peak bone mass during adolescence is one of the most important strategies to decrease osteoporotic fractures later in life. Initial bone mass adjusted by height and weight in 10-year-old girl was associated positively with intakes of dairy products and small fish. Annual increase in bone mass from age 10 years to 11 years was associated positively with increased intake of fish, fruit, vegetables, and soybeans. Thus, not only calcium but also adequate dietary patterns such as increased intake of fish, fruit, vegetables, and soy products lead to higher peak bone mass in adolescent and will decrease the risk of bone fracture in postmenopausal age.

Osteoporosis and age-related fracture syndromes.

Osteoporosis is one of the most important age-related diseases. Each year in the United States it causes at least 1.2 million fractures and costs 7 to 10 billion dollars. The main cause of the fractures is increased bone fragility due to low bone density, although in the elderly an increase in the frequency of falls and in the trauma produced by the falls also contributes to fractures. Low bone density in osteoporosis has multiple causes which can be grouped into the categories of low initial bone mass and bone loss due to ageing, menopause, and sporadic factors. Given the magnitude of the problem, prevention is the only cost-effective approach. Enough is known about causes of bone loss leading to osteoporosis that an effective programme of prevention can be designed. Its implementation in the population should substantially reduce the incidence of this major public health problem.

IZMENENIYa KOSTNOY TKANI ChELOVEKA V KOSMIChESKOM POLETE II. NEKOTORYE ZAKONOMERNOSTI I OSOBENNOSTI

There are considered possible mechanisms of some peculiarities of cosmonauts bone tissue changes after space flights 5-7 month duration, that were diagnosed using dual energy X-ray absoptiometry (DEXA). Local osteopenia in spongy bone of the body lower part may be connected with big weight bearing load in 1g conditions. Increasing of mineral content in upper part of the skeleton and hypermineralization of vertebrae body spongy bone, that were showed by computer tomography possible are the secondary effects and are connected with fluid redistribution to cranial direction, including abdomen. Additional negative gradient of bone mass in bones of lower part of skeleton, that is observed in early period of readaptation (till 1 month) may be explained as result of acceleration of bone remodeling (resorption and formation of bone), as reaction to recover of loading. Individual variability of above mentioned reactions is connected with genetically determined initial bone mass and phenotype of bone metabolism. There are considered possibilities of genetic prediction of osteopenia in discussed conditions.

Tail suspension induces bone loss in skeletally mature mice in the C57BL/6J strain but not in the C3H/HeJ strain.

We assessed the effects of tail-suspension in two skeletal genetic backgrounds, the high C3H/HeJ (C3H) and low C57BL/6J (B6) bone masses inbred mice (male, 4-months old). Cancellous bone mass and structural parameters were evaluated in distal femoral metaphysis by three dimensional microcomputed tomography. Bone cellular activities were evaluated by histomorphometry and measurements of alkaline phosphatase activity (ALP) and osteocalcin in blood and deoxypyridinoline (D-pyr) in urine. In C3H mice, 2- and 3-week unloading experiments were performed. After an early and transient decrease in body weight, a 2-week suspension period resulted in stimulation of both bone formation rate by 45% and active osteoclastic surfaces by 19%. D-pyr did not change, but ALP and osteocalcin levels increased by 18% and 72%, respectively, in 2-week suspended mice, and osteocalcin remained elevated by 30% in the 3-week suspended mice. Such cellular modifications allowed the C3H mice to maintain their initial bone mass and trabecular structural parameters even after a 3-week suspension period. In B6 mice, 1- and 2-week unloading experiments were performed. Tail suspension resulted in decreased body weight during the first days followed by an incomplete recovery during the second week of unloading. The resorption activity was unaffected by any suspension time period, whereas a decrease of 42.5% in bone formation rate and of 21.5% in ALP were seen by the end of the first week of suspension, both values being restored after a 2-week suspension period. At this latter time, trabeculae were thinner, leading to a 24.5% cancellous bone loss. Trabecular number and connectivity, rod-plate index, and degree of anisotropy were not modified. We concluded that C3H mice constituted a unique model in which genetic background overwhelmed the usual effects of reduced biomechanical usage in bone, whereas B6 mice, compared with the standardized rat model, offered an alternative model of bone loss in a mature skeleton.

THE EFFECT OF GUI-ZHI-JIA-SHU-FU-TANG, IPRIFLAVONE AND OXAPROZINE ON MAINTENANCE OF BONE MASS AND LOW BACK PAIN IN PATIENTS WITH OSTEOPOROSIS

Recently seen an increasing number of patients with osteoporosis has been observed that presents as a chronic illness, particularly to the elderly female patients. It is important not only to treat pain but to follow up bone mass changes to prevent decrease in bone mass. On a measurement of bone mass in patients with osteoporosis, author has emploied the Microdensitometry (MD) method. In this study, author examined changes of bone mass and the severity of pain in patients on long-term therapy with Gui-zhi-jia-shu-fu-tang, Ipriflavone and Oxaprozine.In 18 cases given Gui-zhi-jia-shu-fu-tang, the initial bone mass data were as follows : metacarpal-index (MCI), 0.39±0.08; bone density (ΣGS/D), 2.07±0.32. No difference or increase from the initial values after three, six and nine months of treatment was observed.In 22 cases given Ipriflavone, the initial data were : MCI, 0.39±0.07;ΣGS/D2.07±0.33. The results obtained after three, six and nine months of treatment showed no difference or increase from the initial values.In 11 cases given Oxaprozine, the initial MCI and ΣGS/D values were 0.40±0.06 and 2.08±0.33, respectively. Furthermore, these data were 0.36±0.05 and 1.92±0.26 after nine months, showing a significant decrease.The severity of pain was equally reduced by treatment with Gui-zhi-jia-shu-fu-tang or Oxaprozine. However, only the bone mass in patients given Oxaprozine was decreased.The group given Gui-zhi-jia-shu-fu-tang showed suppression of bone loss, demonstrating the effectiveness of this agent in maintaining and improving bone mass.

The different routes of administration and the effect of hormone replacement therapy on osteoporosis

To review osteoporosis, a disease characterized by low bone mass, microarchitectural deterioration of bone tissue leading to increased bone fragility and a consequent increase in fracture risk. The disorder has become a major health problem in the West, where increased life expectancy has placed new emphasis on disorders related to aging.Review of selected literature.Bone mass increases rapidly in growing children and adolescents, reaching a peak in adults in their 20s and 30s. After 35 to 45 years of age, bone mass begins to decline slowly. Men lose bone mass at approximately the same rate over their lifetime; in women, however, the rate of bone loss increases dramatically after their menopause, whether it is natural or surgical. It is also important to note that bone mass in women below the age of 50 is just two thirds of that found in men. These two factors--the low initial adult bone mass and the more rapid bone loss--combine to produce a high incidence of osteoporosis in elderly women. Significant morbidity and mortality are attributed to osteoporosis-related fractures, underlining the importance of new therapeutic and preventive modalities being evaluated and applied in high-risk populations. In adult women before the onset of menopause, rates of bone formation and bone resorption are approximately equal; calcium balance is maintained, and no loss of bone mass occurs. But after menopause, although both bone formation and bone resorption rates increase, the rate of bone resorption increase more rapidly, resulting in calcium imbalance and a net loss of bone. The first goal of therapy for osteoporosis is thus the restoration of bone resorption and bone formation to premenopausal levels. Optimally, bone formation may be maintained at a slightly higher level than that of bone resorption, producing a positive calcium balance.

Users of low-dose glucocorticoids have increased bone loss rates: A longitudinal study

Although high doses of glucocorticoids are believed to cause bone loss, the effects of low glucocorticoid doses are still controversial. Our study examined the effects of low-dose glucocorticoids on the rate of bone loss at three appendicular bone sites. The study population was a cohort of elderly Japanese-Americans, 1094 women and 1378 men. The women were all postmenopausal. At the baseline examination the mean age of the women was 64 years (range 45-81), and the mean age of the men was 68 years (range 61-82). Glucocorticoid users (19 women and 21 men) had used oral systemic or inhaled glucocorticoids on a regular schedule for more than 1 month (mean use was 2.1 years for the women and 1.9 years for the men). The most common dose was equivalent to 5 mg/day of prednisone; fewer than 15% of users had taken doses equivalent to 10 mg/day or more. Changes in bone mass at the calcaneus, distal radius, and proximal radius were documented using bone densitometry at 1 to 2-year intervals over an 8-year period. The initial bone mass of the glucocorticoid users and controls was similar at the baseline examination. The subsequent loss rates among females during glucocorticoid use, however, were approximately double that of the controls. Among males, bone loss rates during glucocorticoid use were 2-3 times that of controls for the calcaneus and radius sites. The differences between glucocorticoid users and controls persisted after adjusting for confounding variables such as age and use of thiazides and estrogens.(ABSTRACT TRUNCATED AT 250 WORDS)

Salmon calcitonin reduces vertebral bone loss in glucocorticoid-treated beagles.

Glucocorticoids induce bone loss by increasing bone resorption and decreasing bone formation. In this study we have investigated the potential of salmon calcitonin to attenuate glucocorticoid-induced bone loss in a dog model. Male beagles were divided into three groups: 1) untreated controls, 2) prednisone-treated dogs (1 mg.kg-1.day-1 orally), and 3) prednisone-calcitonin-treated dogs (1.5 U.kg-1.day-1 calcitonin subcutaneously and 1 mg.kg-1.day-1 prednisone orally). Assessment of bone mass by dual energy X-ray absorptiometry demonstrated that bone density remained stable in controls throughout 48 wk. Prednisone-treated dogs lost 13.2% of their initial bone mass by 48 wk. Concomitant calcitonin treatment attenuated prednisone-induced bone loss to only 3.2% at 48 wk. Bone histomorphometry of the spine showed reduced trabecular bone volume in prednisone-treated dogs, whereas control and prednisone-calcitonin-treated animals maintained normal trabecular bone volume. Both prednisone- and prednisone-calcitonin-treated dogs acquired a defect in osteoblastic function as evidenced by a reduction in mean wall thickness and trabecular thickness. Thus calcitonin attenuates the early bone loss induced by glucocorticoids. However, calcitonin failed to prevent glucocorticoid-induced osteoblast dysfunction.

Physical activity and bone mass: exercises in futility?

Growing bone responds to low or moderate exercise through significant additions of new bone in both cortical and trabecular moieties and results in adaptation through periosteal expansion and endocortical contraction. Intracortical activation frequency declines in growing bone in response to exercise, reducing porosity and the remodelling space. These adaptations can be maintained into and throughout adulthood. Young bones have a greater potential for periosteal expansion than aging bone, allowing them to adapt more rapidly and efficiently to an acute need for increased strength, but a threshold level of activity exists above which some bones respond negatively by suppressing normal growth and modelling activity, reducing geometric, mechanical and material properties in cortical and trabecular bone. From cross-sectional studies, differences in bone mass between exercising and non-exercising adults are generally less than 10%, but do not account for exercise history which may be very important, and often fail to consider important confounding variables. There is sufficient longitudinal data to demonstrate that moderate to intensive training can bring about modest increases of about 1-3% in bone mineral content (BMC) of men and premenopausal women. In young adults very strenuous training may increase BMC of the tibia up to 11% and its bone density (BD) by 7%, but may represent periosteal woven bone formation in response to excessive strain. Some evidence shows that exercise can also add bone mass to the post-menopausal skeleton, although the amounts are site-specific and relatively modest. Increases as high as 5-8% can be found after 1-2 years of intensive exercise, but additions of bone to the femur and radius are generally less than 2%, well within the range of the remodelling space and measurement precision. Although increases in bone mass of the post-menopausal skeleton may be extremely modest, physical activity is important to preserve bone mass and muscle function. Detraining reduces any bone mass increase to pre-existing values so that long-term benefits are only retained with continuing exercise. Most importantly, the amount of bone gain that can be achieved appears dependent primarily on the initial bone mass suggesting that individuals with extremely low initial bone mass may have more to gain from exercise than those with moderately reduced bone mass.

Change in bone mass immediately before menopause.

A group of 75 healthy women nearing menopause were entered into a longitudinal study of bone mass and bone cell function. All were at least 46 years, were still menstruating, and had premenopausal levels of follicle stimulating hormone (FSH) and estradiol (E2). Bone density measurements of the spine (dual-photon absorptiometry, DPA) and total-body (DPA) and forearm (single-photon absorptiometry, SPA) were made at 6 month intervals along with measurements of FSH and E2 over an average of 2.04 +/- 0.45 years. The annual rate of change in bone mass was determined for each individual by regressing the bone mass measurement at each site at the time of observation. The slopes were pooled, and the percentage annual change was calculated as the mean slope divided by the initial mean bone mass value. The mean rates of change in bone mass were calculated with and without weighting by length of observation. No meaningful differences in the results were seen in the weighted values compared to the unweighted values, and none of the sites showed a slope significantly different from zero. Demonstrated reproducibility and sample size provided sufficient power to detect annual weighted rates of change of 0.81% for spine BMC, 0.69% for spine BMD, 1.31% for forearm BMC, 1.55% for forearm BMC/BW, and 1.09% for total body bone mineral. We conclude that if changes in bone mineral are occurring in women at this age, they are substantially less than 1%/year for spine and not much more for the forearm or total skeleton.

Relationship between bone mass and rates of bone change at appendicular measurement sites.

The rate of bone change among postmenopausal women may vary depending upon the initial bone mass. Examining this possibility is difficult, however, because of a negative statistical bias that occurs when change is regressed against the initial value of the same variable. In this article, four statistical methods were applied to measure the association between bone mass and the rate of bone change. The study population was Japanese-American women, who were monitored for approximately 5 years. Bone changes were determined for the calcaneus and the distal and proximal radius. The results were consistent across the bone sites but differed between statistical methods. Three of the four methods indicated that the women with the greater bone mass had the greater loss rates. The fourth method did not support this association. Possible reasons for the discordant results are discussed. Using the "best" estimate of the relationship, a gradual convergence of bone mass was projected over time toward the population mean. The convergence occurred because women with higher bone mass had a somewhat faster loss rate than women with lower bone mass. Overall, however, the variation in bone mass between individuals was large compared to the rate of convergence.

The impact of menopausal age on future fragility fracture risk

Altogether 733 postmenopausal women were interviewed with regard to their age at menopause. Subsequent fragility fractures over an 11 year period were recorded. Fragility fractures had occurred in 212 women. These women had an earlier menopause, but the deviation from the nonfracture group was significant only in those who were less than 70 years at the beginning of the fracture catchment period. Women 50-69 years of age, in the lowest quartile of menopausal age, sustained 50% more fragility fractures than those in the highest quartile. In older women menopausal age does not predict fragility fractures. Women less than 70 with an early menopause had a significantly lower initial bone mass.

The predictive value of bone loss for fragility fractures in women: A longitudinal study over 15 years

Fifteen years after their forearm bone mineral content was measured, 366 women were measured again with the same single photon technique. 96 of the women had sustained one or more fragility fractures during that period. The initial bone mineral content was less in those women who were to have fractures. The rate of loss over the years did not differ between fracture and non-fracture women--the initial bone mass was the better predictor. Peak bone mass in the women in this study occurred before the age of 40.

Use of nasally administered salmon calcitonin in preventing bone loss

This article reviews several of our studies in which we evaluated the effect of nasal salmon calcitonin in preventing bone loss in normal women just after menopause. In the first study, after treatment with nasal salmon calcitonin, bone loss stopped and, in fact, actually increased slightly. In contrast, the placebo group continued to lose bone mass. On the other hand, bone mass in the forearm, which has more cortical bone, showed no change in response to nasal salmon calcitonin. The effect of salmon calcitonin nasal spray in women with established osteoporosis has also been studied. In one study, bone mass in the forearm was constant in the group receiving nasal salmon calcitonin plus calcium, whereas bone mass in the placebo plus calcium group decreased by roughly 2%. Similarly, patients in the group without any treatment also lost 2%. The effect of nasal salmon calcitonin is probably the result of a reduction in the bone resorption to a level seen in premenopausal females. When women were divided according to their baseline bone turnover or initial bone mass, the women with the highest turnover level (assessed by alkaline phosphatase or fasting urinary hydroxyproline) or the lowest bone mass were the group with the greatest increase in bone mass. In conclusion, treatment with salmon calcitonin nasal spray in patients with established osteoporosis stops bone loss, normalizes bone turnover, and causes no subjective or objective side effects.

Attainment of Peak Bone Mass

Most physicians are aware of the inexorable loss of bone that accompanies aging. Osteoporosis is one consequence of this loss. The bone density of elderly women, who manifest osteoporotic fractures, depends on both the rate of loss and the initial bone mass. Attention to the factors that lead to the development of peak bone mass, which is the highest value that an individual attains during her lifetime, is warranted. The large variance of normal bone density is often not appreciated. A normal 30-yr-old woman in the bottom decile for bone density could have the same density as an 80-yr-old woman in the top decile. The variance does not appear to increase with aging; and because the normal range in young women is already so broad, inequities must be present during growth. Not surprisingly, the list of factors relating to peak bone mass is similar to the list of risk factors for postmenopausal osteoporosis, including race, sex, heredity, diet, hormonal factors, activity, weight, and drugs or diseases that lead to bone loss. Unfortunately, these factors are not understood, not well studied, and not at all independent. There is no consensus on the age at which peak bone mass occurs. Longitudinal measurements of bone density through adolescence and early adult years are not available. Some cross-sectional studies have found no increase in bone density after age 20, whereas others, with larger numbers of subjects, find the bone density increases until about age 35, then starts a downward trend (1). Thus, it appears that the density of the bone continues to increase for at least a decade after the maximum height has been attained. Hereditary and racial factors are probably the most important determinants of peak bone density. Black children have higher bone density than white children (2). The bone density of teenage girls is correlated to the densities of the fathers and mothers (3). Twin studies have given the best data about the influence of heredity on bone mass. Pocock et al. (4) showed that bone density was significantly better correlated in monozygotic than in dizygotic twins. How the genetic message governs the bone density is unknown. Bone density is related to body size, muscle mass, and hormone levels, all of which are also under genetic control, but these known factors do

The contribution of bone loss to postmenopausal osteoporosis

We have addressed the relative importance of peak bone mass and subsequent rate of loss in determining postmenopausal women's bone mass in old age, by examining longitudinal measurements of radial mid-shaft bone mass on various samples of healthy white postmenopausal women. Using both the variance estimate of age-specific rates of bone loss and the population variance in bone mass, we determined that rates of loss could contribute importantly to future bone mass. However, since we found a small negative correlation between initial bone mass and rate of loss, it was necessary to estimate the effect of bone loss as the complement of the contribution of initial bone mass. We found that the influence of bone loss (relative to initial bone mass) increases as the women age, such that by about age 70, the contribution of initial bone mass and rate of loss approached equality. However, estimated rates of bone loss were not very stable over time, so it was difficult to identify long-term 'fast-losers'. We conclude that the rate of postmenopausal bone loss is an important contributor to osteoporosis at old age, but it is difficult to identify long-term fast-losers, thereby reducing the clinical value of assessments of rates of change in bone mass early in the postmenopause.

The concept and treatment of osteoporosis

Osteoporosis is a dynamic process, thought to be caused by an uncoupling between osteoblast and osteoclast activity. Altered pulsatile secretion of growth hormone and parathyroid hormone (PTH) have been proposed as pathogenetic factors for this unbalanced coupling. The anatomical lesions are believed to be reversible until trabecular perforations develop, if fractures already occured the anatomical defect is permanent. It is helpful to classify osteoporosis in stages of increasing severity depending on bone density and the presence of fractures. Theoretically, if the bone density is above the fracture threshold, then the only therapeutic goal is to maintain the bone mass. If instead the mineral density is below the threshold, an active therapy is needed with drugs that can possibly increase the skeletal mass. Osteoporosis with multiple fractures cannot be reversed. The authors propose a promising pharmacologic treatment for osteoporosis, based on the combination of human PTH-(1–38) and intranasal salmon calcitonin. If started in the early stages of the osteoporotic process, this regimen may restore the initial bone mass. In more advanced stages, only a correction of the metabolic defect is possible, but the irreversible vertebral deformities are not affected. On the basis of the results, cyclic therapy with human PTH-(1–38) and salmon calcitonin represents a good treatment choice for osteoporosis.