Effects of aging on bone mineral content and bone biomarkers in female cynomolgus monkeys.

Age-related changes in bone mineral content and bone biomarkers were assessed over the complete lifespan of female cynomolgus monkeys. The bone mass of the lumbar spine increased linearly from birth to about 2.5 years of age, and this increase gradually slowed thereafter until a peak bone mass was achieved at 9 years of age. The bone mass stabilized after 9 years of age, showing no sign of further reduction with age. In contrast with the significant increase in bone mass before 2.5 years of age, significant decreases occurred in the serum concentrations of the following bone formation markers: intact osteocalcin, bone-specific alkaline phosphatase and amino-terminal propeptide of type I procollagen, but the serum concentration of carboxy-terminal propeptide of type I procollagen did not change significantly throughout the entire lifespan. Concerning the bone resorption markers, the levels of tartrate-resistant acid phosphatase fluctuated throughout the entire lifespan. The skeleton of an aging female monkey undergoes changes similar to those observed in senescent humans, but did not undergo the menopausal changes seen in women. The use of female cynomolgus monkeys to model human skeletal interventions should therefore be undertaken with consideration of the similarities and differences between cynomolgus monkeys and humans.     

Changing the structurally effective mineral content of bone with in vitro fluoride treatment

Bovine femur cortical bone specimens were tested in tension after being treated in vitro for 3 days with sodium fluoride solutions of different molarity (0.145, 0.5, and 2.0M). The treatments alter the mechanical properties of the bone samples with different degrees as compared to control samples (untreated). The mechanical properties of the treated samples have lower elastic modulus, yield and ultimate stress, acoustic impedance and hardness, and higher ultimate strain and toughness as compared to control samples. The observed effects were intensified with the increasing molarity of the treatment solutions. This study shows that the fluoride treatment can be used to investigate the composite behavior of bone tissue by altering the structurally important bone mineral content in a controlled manner.     

Influence of insulin-like growth factor-1 and leptin on bone mineral content in healthy premenopausal women

The aim of the present investigation was to study the influence of plasma insulin-like growth factor-1 (IGF-1) and leptin levels on bone mineral mass (BMC) and bone mineral density (BMD) in premenopausal women and the relationship between IGF-1 and leptin levels. Two hundred and four healthy women participated in this study. All participants had a body mass index (BMI) <30 kg/m(2) and were matched for their level of mean daily energy expenditure. BMC and BMD were correlated with measured body composition and blood biochemical parameters. No association was observed between BMC and BMD values with measured physical performance characteristics. Leptin had a significant association with BMC (beta = 0.840; P = 0.0001), total BMD (beta = 0.833; P = 0.0001), femoral neck BMD (beta = 0.829; P = 0.0001), and lumbar spine BMD (beta = 0.833; P = 0.0001). However, these associations were no longer independent when adjusted for body fat mass (FM) and trunk fat:leg fat ratio (P > 0.385). IGF-1 was significantly related to BMC (beta = 0.920; P = 0.0001), total BMD (beta = 0.918; P = 0.0001), femoral neck BMD (beta = 0.921; P = 0.0001), and lumbar spine BMD (beta = 0.917; P = 0.0001), but did not remain significant when adjusted for fat free mass (FFM; P > 0.062). In addition, a significant association between IGF-1 and leptin was found (beta = 0.801; P = 0.0001), and it remained significant after controlling for age, FM, FFM, insulin, and fasting insulin resistance index (FIRI), but not when adjusted for BMC and body mass values. In conclusion, it appears that fasting IGF-1 and leptin concentrations have no direct effect on BMC and BMD values. In addition, if there is an important relationship between IGF-1 and leptin, it is mediated or confounded by BMC in premenopausal women.     

Total body bone mineral and pelvis bone mineral content as parameters of bone mass in men. A dual-energy X-ray absorptiometry study.

Total body bone mineral content (TBBM) is a highly discriminating determinant of bone mass. We correlated TBBM with pelvis bone mineral content (PBMC) and pelvis bone mineral density (PBMD) in 179 normal men, in order to observe whether the pelvis is an adequate region of bone mass evaluation. There was a good correlation between PBMC and TBBM (r = 927, p less than 0.001), and significant correlations between PBMD and TBBM (r = 818, p less than 0.001) and between PBMC and PBMD (r = 0.902, p less than 0.001). As the pelvis does not undergo the densitometric changes so often observed in the spine, we believe that the pelvis is appropriate as anatomic region for bone mass evaluation studies.     

Influence of the nest environment on bone mineral content in hatchling painted turtles (Chrysemys picta)

We performed an experiment at a field site in north-central Nebraska to assess the role of the nest environment in inducing variation in bone mineral content in hatchling painted turtles Chrysemys picta (Schneider 1783). The contents of several newly constructed nests were manipulated by reciprocal transplant, after which the eggs were allowed to incubate for 8 wk under natural conditions. The nests were then excavated, and the eggs were brought into the laboratory to complete incubation and hatch under standard conditions of temperature and moisture. The hatchlings were killed, and their carcasses and residual yolks were analyzed separately for calcium and phosphorus. More of the random variation in carcass calcium and phosphorus was related to the nest in which eggs incubated (37% and 42%, respectively) than was associated with the clutch of origin (21% and 37%). Moreover, hatchlings from some nests contained substantially more calcium and phosphorus than did hatchlings from other nests, both in terms of the absolute amounts of the elements in their carcasses (pointing to variation in body size) and in terms of the concentrations of those elements (pointing to variation in bone density). The amounts of calcium and phosphorus in carcasses of hatchlings were positively correlated with changes in mass of their eggs during the 8 wk that the eggs incubated in nests in the field, thereby indicating that the influence of the nest environment on developing embryos probably was mediated by water exchanges experienced by the eggs. These findings indicate that developmental plasticity underlies a major fraction of the variation in mineral content of hatchling painted turtles emerging from nests in the field. Phenotypic variation attributable to plasticity consequently needs to be addressed in models for life-history evolution of painted turtles and other chelonians producing eggs with soft, flexible shells.     

Effects of triiodothyronine and estrogen administration on bone mass, mineral content and bone strength in male rats.

Experimental hyperthyroidism had a negative effect on bone mineral density, but did not significantly alter mechanical properties of femur and femoral bone thickness. Estradiol at a dose used in humans for the treatment of osteoporosis decreased seminal vesicle weight and concentration of testosterone but increased bone density in male rats compared to intact animals. In these rats, the mechanical analysis revealed an increased mechanical femur strength higher than the increase in bone density and femoral cortical thickness. When hyperthyroid male rats with low bone density were treated with estradiol in spite of a low plasma testosterone, the changes in bone density resulting from hyperthyroidism were entirely prevented. Estrogens protect the male skeleton against resorbing action of T (3). Treatment with estradiol in male rats with hyperthyroidism did not increase mechanical bone strength or femoral cortical thickness as it did with estradiol administration alone. Our results suggest that exogenously administered estrogens may have therapeutic value in preventing bone loss accompanying triiodothyronine administration, even in male rats with a low testosterone levels. At the concentration studied, estradiol increased in spite of low plasma testosterone, bone mineral density, mechanical strength of femur, and femoral cortical thickness.     

Effect of bone mineral content on the tensile properties of cortical bone: experiments and theory

The effect of mineral volume fraction on the tensile mechanical properties of cortical bone tissue is investigated by theoretical and experimental means. The mineral content of plexiform, bovine bone was lowered by 18% and 29% by immersion in fluoride solutions for 3 days and 12 days, respectively. The elastic modulus, yield strength and ultimate strength of bone tissue decreased, while the ultimate strain increased with a decrease in mineral content. The mechanical behavior of bone tissue was modeled by using a micromechanical shear lag theory consisting of overlapped mineral platelets reinforcing the organic matrix. The decrease in yield stress, by the 0.002 offset method, of the fluoride treated bones were matched in the theoretical curves by lowering the shear yield stress of the organic matrix. The failure criterion used was based on failure stresses determined from a failure envelope (Mohr's circle), which was constructed using experimental data. It was found that the model predictions of elastic modulus got worse with a decrease in mineral content (being 7.9%, 17.2% and 33.0% higher for the control, 3-day and 12-day fluoride-treated bones). As a result, the developed theory could not fully predict the yield strain of bones with lowered mineral content, being 12.9% and 21.7% lower than the experimental values. The predicted ultimate stresses of the bone tissues with lower mineral contents were within +/- 10% of the experimental values while the ultimate strains were 12.7% and 26.3% lower than the experimental values. Although the model developed in this study did not take into account the presence of hierarchical structures, voids, orientation of collagen molecules and micro cracks, it still indicated that the mechanical properties of the organic matrix depend on bone mineral content.     

The effect of chronic nicotine administration on bone mineral content and bone strength in normal and castrated male rats.

Tobacco, containing nicotine as the principal pharmacologically active chemical, has been identified as being a risk factor for the development of osteoporosis. Thirty-two male Wistar rats of two months of age were castrated or sham operated to evaluate the effects of long-term administration (four months) of nicotine in drinking water (9.0 mg/kg/day). The presence of cotinine in urine confirmed successful delivery of nicotine. The bones were tested mechanically by a three point bending test in a Mini Bionix (MTA) testing system. The bones from castrated rats were characterized by a reduction in bone density as well as ash, calcium and phosphate content. Castration significantly altered mechanical properties of bone (9%) and femoral cortical thickness. When intact rats were treated with a high dose of nicotine, nicotine had negative effect on tibial bone density as well as ash, calcium, phosphate content and significantly altered the mechanical properties of bone (12%) and femoral cortical thickness compared to intact animals. Nicotine itself does not exert any anti-androgenic effect and does not produce changes in the weight of seminal vesicles. Nicotine-induced bone loss is associated with high bone turnover in the male rats as expressed by increased TrACP and B-ALP. When castrated rats were treated with the high dose of nicotine the changes in bone density resulting from castration were not further potentiated. These results document the efficacy of nicotine at high doses to cause bone loss and loss of bone mechanical strength in intact rats. The results of the present study may be interpreted as supporting the hypothesis of nicotine as a risk factor for osteoporosis.     

Effects of nasal calcitonin on bone mineral density following parathyroidectomy in patients with primary hyperparathyroidism

AIM: To investigate whether nasal salmon calcitonin (CT; 200 U/day) given in addition to calcium helps to restore the bone mass after parathyroidectomy (PTX) in patients with primary hyperparathyroidism (PHPT). METHODS: Twenty patients with PHPT were enrolled after successful PTX and received 1 g calcium per os daily for 1 year. They were randomly assigned either to nasal CT (CT group) or to no treatment. The bone mass was measured using dual-energy X-ray absorptiometry at multiple sites. RESULTS: Eight patients in each group completed the study. After 12 months, the bone mass increased significantly at whole-body level and at lumbar spine in both groups, increased at hip and epiphyses of tibia or radius in the CT group only, and did not change at diaphyses of tibia and radius in either group. CONCLUSIONS: Bone mass increases after PTX for PHPT in patients receiving oral calcium. CT may help to restore the bone mass at sites of the appendicular skeleton, where trabecular bone predominates.     

Effect of calcitonin treatment on deafness due to Paget's disease of bone.

Seventeen patients with Paget''s disease of the skull and deafness were followed for nine to 18 months. Patients who received calcitonin treatment showed less deterioration in hearing than untreated patients. Calcitonin treatment may retard the progression of deafness in Paget''s disease, and further studies are indicated.     

Measurement of bone mineral content in vivo using photon absorptiometry

Progress in evaluating treatment of systemic bone disease has been hampered in the past by lack of precise in vivo quantitative techniques. Recently a method has been developed for measurement of bone mineral content (BMC), based on bone absorption of low-energy monochromatic radiation. This paper discusses a technique of photon absorptiometry using ¹²⁵l as a collimated point source. The technique is simple, with accuracy and precision within 2%.BMC and bone width (W) were measured in the distal radius of 359 normal subjects ranging in age from 5 to 82 years. A “normal” curve of BMC/W with age as the independent variable was then obtained from this population and was constructed for each sex. A positive correlation of BMC/W with height and body weight was found in a group of normal males.A series of patients with osteoporosis or malabsorption, or undergoing hemodialysis or steroid treatment, was then assessed in order to demonstrate changes in BMC/W that may occur secondary to disease or disturbances in calcium metabolism. Many of these patients were found to have a BMC/W below the normal mean value for their age and sex.     

Annual changes in bone mineral content and body composition during growth

OBJECTIVES: To compute the annual changes in total bone mineral content (BMCt), lean tissue mass and fat mass (LTM and FM) during growth. METHODS: Whole body DXA data were used to calculate the annual changes of the parameter P (P = BMCt, LTM or FM), as a percentage, as DeltaP% = 100 x (P(i+1) - P(i)) / P(i); with P(i) and P(i+1) the values for P at age i and age (i+1). Smoothed curves were then obtained from DeltaP% values plotted against age. RESULTS: Changes in FM were different in males and females. A peak velocity was marked for the three tissues at age 6.5 in boys, and at age 6.5-7.5 in girls; a pubertal peak spurt appeared at age 12 in girls and between age 13 and 14 in boys. This latter peak was followed by an exponential decrease, and no significant changes were found for the three components after age 20 in girls and age 21-22 in boys. CONCLUSION: Changes in tissue accretion during growth are easy to follow when expressed in percentages. Fat changes, especially, should be around 17% in girls and 15% in boys at the age of puberty.     

Effect of subclinical hypothyroidism and obesity on whole-body and regional bone mineral content

OBJECTIVE: The present investigation was aimed to evaluate the effect of subclinical hypothyroidism and obesity on bone mineral content (BMC) in different body segments. METHODS: Thirty-two premenopausal women (age: 37 +/- 9.9 years), with a wide range in body mass index (BMI), were studied. Subclinical hypothyroidism was defined by a basal TSH > or = 4 microU/l and/or a TRH-stimulated peak > or = 30 microU/l. For each subject, weight, height, BMI (weight/height(2)) and the waist/hip ratio were measured. Total BMC, total bone mineral density (BMD), leg BMC, leg BMD, trunk BMC, trunk BMD, arm BMC and arm BMD were determined using dual-energy X-ray absorptiometry. Thyroid function (basal and TRH-stimulated TSH, free T(3) and free T(4)) were determined from fasting blood samples for all subjects. RESULTS: Anova was conducted within all the groups to observe the effect of thyroid status and/or obesity on BMC and BMD. There was no statistical difference for age. Total BMC was affected by obesity (p < 0.05) but not by thyroid status, BMD of the legs was significantly influenced both by thyroid function and obesity (p < 0.01); total BMD was affected by hypothyroid status (p < 0.05). A direct relationship between leg BMD and TSH was demonstrated. CONCLUSION: Subclinical thyroid hypofunction and obesity seem to affect BMD differently in the body segments. An influence of gravitational force seems necessary in order to make evident the effect of subclinical hypothyroidism on bone. A condition of subclinical hypothyroidism should be considered when evaluating subjects for osteoporosis, since a BMD measured at the femoral neck may induce underestimation of initial osteoporosis.     

Rationale for the potential use of calcitonin in osteoarthritis

This review provides evidence that osteoarthritis (OA) or a major subset of OA is not only a disease of cartilage but also a disorder of subchondral bone. This review also discusses the potential efficacy of a bone and cartilage active agent, calcitonin, and discusses how calcitonin might be useful in the pharmaceutical treatment of OA.     

Spatio-temporal self-organization of bone mineral metabolism and trabecular structure of primary bone

A nonlinear two-variable reaction-diffusion model of bone mineral metabolism, built from an overall self-oscillatory compartmental model of calcium metabolism in vivo, has been studied for its ability to generate spatial and spatio-temporal self-organizations in a two-dimensional space. Analytical and numerical results confirm the theoretical properties previously described for this kind of model. In particular, it is shown that, for a given set of reactional parameter values and certain values of the ratio of the two diffusion coefficients, there exists a set of unstable wavenumbers leading spontaneously to the development, from the homogeneous steady state, of either different types of stationary spatial patterns (hexagonal, striped and re-entrant hexagonal patterns) or more or less complex spatio-temporal expressions. We discuss the relevance of analogies established between some spatial or spatio-temporal structures predicted by the model and some peculiar features of the primary bone trabecular architecture which appear during embryonic ossification.     

Chronic treatment of Paget's disease of bone with synthetic human calcitonin.

Twelve patients with Paget''s disease of bone were treated with synthetic human calcitonin for seven to 26 months (mean 15.3 months). This group included six patients who had previous therapy. Eleven of the 12 patients experienced relief of the symptoms associated with Paget''s disease. The initial therapy of synthetic human calcitonin 0.5-1.0 mg subcutaneously was administered daily until the alkaline phosphatase had declined to a plateau response; the dose was then decreased to thrice weekly. The major biochemical findings were a 47 percent fall in serum alkaline phosphatase and a comparable decline in 24-hour urinary hydroxyproline. Two subjects discontinued therapy because of side effects; persistent nausea and vomiting in one and a cutaneous allergic reaction in the other. Other side effects were minor. Preliminary results suggest that some patients will maintain the same biochemical response on the reduced dose but that this is not predictable by pre-treatment data. We conclude that synthetic human calcitonin is a safe and effective treatment for Paget''s disease of bone. Preliminary results suggest that the dose and frequency of administration of this agent must be individualized.