Cadmium, osteoporosis and calcium metabolism

Occupational exposure to cadmium has for long been associated with renal tubular cell dysfunction, osteomalacia with osteoporosis, hypercalciuria and renal stone formation. High environmental exposure in Japan resulting from a stable diet of cadmium contaminated rice caused itai-itai disease, fractures occurring mainly in elderly multiparous women, with a form of osteomalacia, osteoporosis and renal dysfunction. More recently a population based study in Europe, in the vicinity of zinc smelters has shown that low to moderate exposure to cadmium, with a mean urinary excretion of cadmium of the order of 1 microg/g creatinine has been associated with a decrease in bone density, an increased risk of bone fractures in women and of height loss in men. In a population-based study of residents near a cadmium smelter in China, forearm bone density was shown to decrease linearly with age and urinary cadmium in both sexes, suggesting a dose effect relationship between cadmium dose and bone mineral density. A marked increase in the prevalence of fractures was shown in the cadmium-polluted area in both sexes. Concentrations of cadmium in blood and urine were taken as exposure biomarkers, and beta2-microglobulin, retinol binding protein and albumin as biomarkers of effect. A marked dose response relationship between these indicators of exposure and effect was shown. Hypercalciuria, which may progress to osteoporosis, has been taken as a sensitive renal-tubular biomarker of a low level of cadmium exposure. Cadmium may also act directly on bone. Animal studies have shown cadmium to stimulate the formation and activity of osteoclasts, breaking down the collagen matrix in bone. Osteoporosis is the main cause of fracures in post-menopausal women, a common occurrence worldwide, giving rise to disability and a high cost to health services. The identification of cadmium, an environmental pollutant, as one causal factor is highly significant in helping to control the incidence of this complex condition.     

Effects of Cadmium on Bone Mineral Density in the Distal and Proximal Forearm: Two Female Population Studies in China

Long-term cadmium exposure may cause bone loss in distal or proximal sites in the forearm. In this study, we observed the effects of cadmium on bone mineral density in both distal and proximal sites in the forearm in two female populations. A total of 456 women living in two different areas participated. All of the participants completed a questionnaire, and the bone mineral density was measured in both the distal and proximal forearm by dual-energy X-ray absorptiometry. Urine samples were collected for the determination of urinary cadmium (UCd). UCd levels were significantly higher in the polluted group than the control group. The bone mineral density of the proximal forearm of subjects in polluted group or with high UCd levels was significantly lower than that of subjects in the control group or with low UCd levels. However, regarding bone mineral density of the distal forearm, this trend was only found in subjects living in area A. Our data showed that cortical bone mineral density in the forearm may be more strongly affected by cadmium exposure than trabecular bone mineral density.     

Low level cadmium exposure, renal and bone effects - the OSCAR study

It is well known that high cadmium exposure causes renal damage, osteoporosis and osteomalacia, whereas the dose-response relationships at low-level exposure are less well established. WHO estimated (1992) that a urinary excretion of 10 nmol/mmol creatinine would constitute a 'critical limit' below which kidney damage would not occur. Later, Belgian and Swedish studies have shown signs of cadmium induced kidney dysfunction in the general population already at urinary cadmium levels around 2-3 nmol/mmol creatinine. The Swedish OSCAR (OSteoporosis-CAdmium as a Risk factor) study comprised 1021 individuals, exposed to cadmium in the environment. Blood and urinary cadmium were used as dose estimates. Protein HC (alpha-1-microglobulin) was used as an indicator of renal tubular damage. Forearm bone mineral density (BMD) was assessed with DXA (dual energy x-ray absorptiometry) technique. The study showed that tubular proteinuria occurred at much lower levels of cadmium dose than previously known. A negative dose-effect relationship was found between cadmium dose and BMD for people at the age of 60 or older. In this age group, there was also a dose-response relationship, showing a three-fold increased risk of low BMD in the group with urinary cadmium over 3 nmol/mol creatinine, as compared to the lowest dose group. There was also evidence of an increased risk of forearm fractures with increasing cadmium levels in the population 50 years of age or older. The potential public health consequences of low level cadmium exposure should be recognized, and measures taken to reduce cadmium exposure to an absolute minimum.     

Comparison of mandibular bone mineral density in osteoporotic, osteopenic and normal elderly edentulous subjects measured by the dual-energy X-ray absorptiometry technique

doi: 10.1111/j.1741‐2358.2012.00625.x Comparison of mandibular bone mineral density in osteoporotic, osteopenic and normal elderly edentulous subjects measured by the dual‐energy X‐ray absorptiometry technique Objective: The aim of this study was to compare the mandibular body bone mineral density according to bone mineral density status of spine and femur measured by dual‐energy X‐ray absorptiometry (DXA) technique in elderly edentulous individuals. Background: One of the factors that affect the survival rate of implants is bone mineral density (BMD) of the jaws. Materials and methods: Fifty edentulous elderly patients’ (27 women and 23 men) spine, femur and the mandibular body BMDs were measured using DXA technique. BMD scans of the AP lumbar spine (L2–L3) and femur were classified using World Health Organisation criteria for bone mass. Results: There was a statistically significant difference between the normal femur group’s–osteoporosis group’s mandibular body BMD (p = 0.001) and femoral osteopaenia group’s–osteoporosis group’s mandibular body BMD (p < 0.001). The femoral osteoporosis group’s mandibular body BMDs were lower than those of both the normal femoral and the femoral osteopaenia group subjects’. Conclusion: Classification of edentulous mandibles according to low and high bone mineral densities is a problem in implant dentistry. The results of this study demonstrated that femoral bone mineral density status may be used to provide preliminary information about the bone mineral density of the mandibular body region in elderly edentulous subjects.     

Effects of 0.4 T rotating magnetic field exposure on density, strength, calcium and metabolism of rat thigh bones

The current study investigated the effects of 0.4 T rotary non-uniform magnetic field (RMF) exposure on bone density in ovariectomized (OVX) rats. Results showed that many bone indexes are significantly elevated after RMF exposure compared to the control OVX group and confirmed mechanistic evidence that strong magnetic field (MF) exposure could effectively increase bone density and might be used to treat osteoporosis. Synergy of daily RMF exposure (30 min a day for 30 days using an 8 Hz rotary 0.4 T MF) with calcium supplement tended to increase the indexes of thigh bone density, energy absorption, maximum load, maximum flexibility, and elastic deformation as compared to those of untreated OVX control group. Results also revealed that the indexes of alkaline phosphatase (ALP), serum phosphate, and serum calcium were higher in rats exposed to RMF with calcium than in the untreated OVX control group. Changes in bone mineral density (BMD) and bone mineral content (BMC) were observed in rats for three months including the first month RMF exposure. Bone density in rats exposed each day for 60 min increased during 1-month exposure and continued to increase during the post-exposure period. Furthermore, bone density and calcium content in rats exposed for 90 min daily decreased initially in the exposure month; however, ratio of increase was well above the control values by the end of the post-exposure period suggesting possible window and delayed effects. The study indicated that RMF exposure to both male and OVX female rats for 120 min a day over 15 day period should effectively promote increase of bone calcium contents (BCC) and bone-specific alkaline phosphatase (BAP) in rats thigh bone as well as a corresponding decrease in deoxypyridinoline crosslinks (DPD).     

Combined treatment with dexamethasone and raloxifene totally abrogates osteoporosis and joint destruction in experimental postmenopausal arthritis

Introduction  

Postmenopausal patients with rheumatoid arthritis (RA) are often treated with corticosteroids. Loss of estrogen, the inflammatory disease and exposure to corticosteroids all contribute to the development of osteoporosis. Therefore, our aim was to investigate if addition of the selective estrogen receptor modulator raloxifene, or estradiol, could prevent loss of bone mineral density in ovariectomized and dexamethasone treated mice with collagen-induced arthritis (CIA).     

Seasonality of VAM infection in three populations of Agrostis capillaris (Gramineae) on soil with or without heavy metal enrichment

Three populations of the perennial grass Agrostis capillaris, growing on limestone derived clay with and without natural enrichment of the heavy metals cadmium, lead, and zinc, and on a sandy soil polluted by a metal smelter have been investigated with regard to the percentage and seasonality of infection with vesicular-arbuscular mycorrhizal (VAM) fungi and its impact on mineral nutrition.In all populations VAM infection was lowest during winter, and highest during late summer and autumn. The population at the metal smelter site was less infected by VAM fungi than both other populations. The concentration of mineral nutrients for the three populations was clearly related to the soil concentration, but hardly modified by the degree of VAM infection.     

Near‐infrared bone densitometry: A feasibility study on distal radius measurement

Osteoporosis, defined as decreased bone mineral density (BMD), poses patients in dangers for fracture risk and has become a major public health problem worldwide because of is associated morbidity, mortality and costs. Without doubt, early detection and timely intervention are important to successfully manage osteoporosis and its associated complications. The dual‐energy x‐ray absorptiometry (DXA) is the most popular and standard method to measure BMD. However, limitations including radiation exposure and availability restrict its application for osteoporosis screening among general population. In this study, we developed a simple method to detect human distal radius bone density based on near infrared (NIR) image system. Among 10 volunteers (including 5 young and 5 elderly participants) receiving bone density measurement using our NIR image system at the ultradistal part of bilateral distal radius, we demonstrated a strong correlation between the optical attenuation and BMD measured with DXA, which may facilitate predicting bone density status. We hope our potential NIR image system may open a new avenue for development of osteoporosis screening facilities and help in prevention of osteoporosis related fracture and its associated complications in the near future. Pearson's correlations between BMD values from the DXA and light intensity of NIR system.      

Extreme obesity reduces bone mineral density: complementary evidence from mice and women

Objective: To evaluate the effects of body adiposity on bone mineral density in the presence and absence of ovarian hormones in female mice and postmenopausal women. Research Methods and Procedures: We assessed percentage body fat, serum leptin levels, and bone mineral density in ovariectomized and non‐ovariectomized C57BL/6 female mice that had been fed various calorically dense diets to induce body weight profiles ranging from lean to very obese. Additionally, we assessed percentage body fat and whole body bone mineral density in 37 overweight and extremely obese postmenopausal women from the Women's Contraceptive and Reproductive Experiences study. Results: In mice, higher levels of body adiposity (>40% body fat) were associated with lower bone mineral density in ovariectomized C57BL/6 female mice. A similar trend was observed in a small sample of postmenopausal women. Discussion: The complementary studies in mice and women suggest that extreme obesity in postmenopausal women may be associated with reduced bone mineral density. Thus, extreme obesity (BMI > 40 kg/m²) may increase the risk for osteopenia and osteoporosis. Given the obesity epidemic in the U.S. and in many other countries, and, in particular, the rising number of extremely obese adult women, increased attention should be drawn to the significant and interrelated public health issues of obesity and osteoporosis.     

Electromagnetic effects on forearm disuse osteopenia: a randomized, double-blind, sham-controlled study

A randomized, double‐blind, sham‐controlled, feasibility and dosing study was undertaken to determine if a common pulsing electromagnetic field (PEMF) treatment could moderate the substantial osteopenia that occurs after forearm disuse. Ninety‐nine subjects were randomized into four groups after a distal radius fracture, or carpal surgery requiring immobilization in a cast. Active or identical sham PEMF transducers were worn on the distal forearm for 1, 2, or 4 h/day for 8 weeks starting after cast removal (“baseline”) when bone density continues to decline. Bone mineral density (BMD) and bone geometry were measured in the distal forearm by dual energy X‐ray absorptiometry (DXA) and peripheral quantitative computed tomography (pQCT) at entry (“baseline”) and 8, 16, and 24 weeks later. Significant average BMD losses after baseline were observed in the affected forearm at all time points (5–7% distally and 3–4% for the radius/ulna shaft). However, after adjusting for age, gender, and baseline BMD there was no evidence of a positive effect of active versus sham PEMF treatment on bone loss by DXA or pQCT for subjects completing all visits (n = 82, ～20 per group) and for an intent‐to‐treat analysis (n = 99). Regardless of PEMF exposure, serum bone‐specific alkaline phosphatase (BSAP) was normal at baseline and 8 weeks, while serum c‐terminal collagen teleopeptide (CTX‐1) was markedly elevated at baseline and less so at 8 weeks. Although there was substantial variability in disuse osteopenia, these results suggested that the particular PEMF waveform and durations applied did not affect the continuing substantial disuse bone loss in these subjects. Bioelectromagnetics 32:273–282, 2011. © 2010 Wiley‐Liss, Inc.     

绝经后健康妇女甲状旁腺激素基因多态性与骨密度的关系

利用限制性片段长度多态性分析（RFLP）研究北京地区绝经后妇女甲状旁腺激素（PTH）基因多态性与骨密度的关系。筛选健康、无亲缘关系的绝经后妇女185例, 应用双能X射线骨密度仪（DEXA）检测腰椎等部位的骨密度,用PCR-RFLP方法检测绝经后妇女的PTH基因型。绝经后健康妇女中bb、Bb、BB三种基因型的分布频率分别为7.56%、28.11%和64.32%。方差分析显示前臂部位骨密度与PTH基因相关。除华氏三角区外,BB基因型各部位的骨密度值均高于Bb、bb基因型。Logistic回归分析结果显示,bb基因型组骨质疏松与正常妇女存在显著差异（P＜0.001）。 PTH基因中B基因型可能对维持骨量具有一定的作用。     

Short-term Administration of Water-soluble Silicon Improves Mineral Density of the Femur and Tibia in Ovariectomized Rats

Silicon is important for the proper growth and development of bone and connective tissues. This study was designed to investigate if water-soluble silicon could be used for the treatment of postmenopausal osteoporosis. Silicon (Si 20 mg/kg body weight/day) was administrated orally to 17-week-old ovariectomized (OVX) rats for 4 weeks. Silicon did not alter weight gain in OVX rats. Silicon supplementation significantly increased the bone mineral density of the femur (p < 0.05, vs. OVX control group) and tibia in OVX rats (p < 0.05, vs. OVX control group). Serum alkaline phosphatase and osteocalcin, two bone formation biomarkers tested, were not significantly altered, but urinary calcium and phosphorous excretion tended to decrease with silicon supplementation. OVX rats with silicon supplementation showed a relatively higher serum CTx compared to the nonsupplemented OVX group (p < 0.01, vs. OVX control group). According to these results, short-term soluble silicon supplementation improved bone mineral density in OVX-induced osteoporosis.     

Bone mineral density in chimpanzees,humans, and Japanese macaques

We performed a comparative study of bone mechanical properties in the radii of chimpanzees (Pan troglodytes), humans (Homo sapiens), and Japanese macaques (Macaca fuscata) using peripheral quantitative computed tomography. We investigated: (1)cortical bone area relative to the total periosteal area (PrA); (2) trabecular bone area relative to PrA; (3) cortical bone density; and (4) trabecular bone density. The cortical bone area index for chimpanzees was almost the same as that of Japanese macaques, whereas the equivalent value in humans was about the two-fifths that of the others. Values for the other three properties were constant among these three catarrhine species. Chimpanzees do not particularly resemble humans, but are more similar to digitigrade macaques in terms of bone properties. The constant trabecular bone area index and trabecular density value in these species may suggest that a certain amount of trabecular bone (20–30% of total bone area at the distal 4% level of the forearm) is necessary to achieve normal bone turnover. The physiological metabolism of bone, including cortical bone density, might be conserved in these catarrhines. Electronic Publication     

Renal dysfunction of cadmium-exposed workers residing in a cadmium-polluted environment

Human exposure to cadmium may occur in both occupational and general environments. We were interested in determining whether a combination of occupational and environmental exposure to cadmium results in different levels of severity of renal dysfunction relative to that arising from environmental or occupational exposure alone. We selected 44 residents, who once were employed in a smelter and lived in a cadmium-polluted area, as group A. Another 88 subjects, who never worked in the plant, but lived in the same area, were selected as group B. Group C consisted of 88 subjects who had no history of occupational exposure to cadmium and lived in a non-cadmium-polluted area. Statistical analysis demonstrated that there was no significant difference in age or gender among the three groups, nor were there significant differences in smoking habits. The prevalence of renal dysfunction as indicated by increased excretion of beta2-microglobulin (B2M), N-acetyl-beta-D-glucosaminidase (NAG) and albumin (ALB), was higher in group A than in group B. This finding suggests that exposure to cadmium both occupationally and environmentally results in a higher prevalence of renal dysfunction, relative to those who are exposed to cadmium only in the general environment. Therefore, this specific population, who once were occupationally exposed to cadmium and lived in polluted areas, should be identified. Furthermore, health examinations of this population should be conducted in time to prevent further health damage induced by cadmium exposure.     

Combined Effects of Fluoride and Cadmium on Liver and Kidney Function in Male Rats

Although cadmium (Cd) and fluoride may both have adverse effects on bone, most studies focus on a single agent. In this study, we investigated the effects of cadmium and fluoride on bone at a relative low level. Sprague–Dawley male rats were assigned randomly into four groups which were given sodium chloride, cadmium (50mg/L), and fluoride (20mg/L) alone, or in combination via drinking water. At the 12th week, urine, blood, and bone tissues were collected for biomarker assay, biomechanical assay, and histological assay. Cadmium had significantly adverse effects on bone mineral density, bone biomechanical property, and bone microstructure. Fluoride slightly increased vertebral bone mineral density but negatively affected bone biomechanical property and bone microstructure. Fluoride could reverse the decrease of vertebral bone mineral density caused by cadmium but could not improve the damage of bone biomechanical property and microstructure caused by cadmium. Tartrate-resistant acid phosphatase 5b levels in rats treated with cadmium and fluoride or in combination were 1–2.5 folds higher than the control. Our data suggest that low level of fluoride could reverse the decrease of vertebral bone mineral density caused by cadmium exposure but has no influence on appendicular skeleton damage caused by cadmium.     

The effect of industrial pollution on Zinc,Cadmium and Copper concentration in the xylem rings of Scot's pine (Pinus sylvestris L.) and in the soil

Summary The concentrations of heavy metals, including zinc, cadmium, and copper were studied in the xylem rings of Pinus sylvestris trees and in the soil of three heavily polluted sites and one non-polluted site. There was a high correlation between the concentration of heavy metals in the soil and recently produced xylem rings. However, the initiation of industrial pollution did not abruptly increase heavy metal concentrations in the xylem rings. There was a high correlation between the zinc content of trees growing near a zinc smelter and the values obtained by other investigators for pine trees growing on the same site.     

Hormone replacement therapy,calcium and vitamin D<Subscript>3</Subscript> versus calcium and vitamin D<Subscript>3</Subscript>alone decreases markers of cartilage and bone metabolism in rheumatoid arthritis: a randomized controlled trial [ISRCTN46523456]

This study aimed to evaluate the effects of hormone replacement therapy (HRT), known to prevent osteoporosis and fractures, on markers of bone and cartilage metabolism. Furthermore, we assessed whether changes in these markers corresponded to alterations in bone mineral density and radiographic joint destructions in postmenopausal women with rheumatoid arthritis. Eighty-eight women were randomized to receive HRT, calcium, and vitamin D3, or calcium and vitamin D3 alone, for 2 years. Bone turnover was studied by analyzing serum levels of C-terminal telopeptide fragments of type I collagen (CTX-I), C-terminal telopeptide of type I collagen (ICTP), bone sialoprotein, and C-terminal propeptide of type I procollagen (PICP) and cartilage turnover by urinary levels of collagen type II C-telopeptide degradation fragments (CTX-II) and cartilage oligomeric matrix protein (COMP) in serum. Treatment with HRT resulted in decrease in CTX-I (P < 0.001), ICTP (P < 0.001), PICP (P < 0.05), COMP (P < 0.01), and CTX-II (P < 0.05) at 2 years. Reductions in CTX-I, ICTP, and PICP were associated with improved bone mineral density. Of the markers tested, CTX-I reflected bone turnover most sensitively; it was reduced by 53 +/- 6% in the patients receiving HRT. Baseline ICTP (P < 0.001), CTX-II (P < 0.01), and COMP (P < 0.05) correlated with the Larsen score. We suggest that biochemical markers of bone and cartilage turnover may provide a useful tool for assessing novel treatment modalities in arthritis, concerning both joint protection and prevention of osteoporosis.     

Densities of microtime rodents along a pollution gradient from a copper-nickel smelter

Population densities of microtine rodents were studied along an air pollution gradient in the Kola Peninsula, Russia, by long-term and short-term trapping. The study area is affected by high sulphur dioxide and heavy metal emissions from the Severonikel copper-nickel smelter in Monchegorsk. The density of Clethrionomys rufocanus, the most abundant vole species in the area, was lowest close to the smelter and increased with distance up to the farthest, less polluted trapping sites. Clethrionomys glareolus, C. rutilus and Lemmus lemmus were absent from the most severely damaged area and were also scarce at the moderately polluted area 28 km south of the smelter. Although the population of C. glareolus has previously been cyclic at the moderately polluted area, we were unable to demonstrate any regular cycle. The most likely explanation for the low number of microtine rodents in the damaged and moderately polluted areas in a decrease in the quantity of important food plants: epiphytic lichens for C. glareolus and possibly C. rutilus, mosses for L. lemmus and seed plants, especially Vaccinium myrtillus, for C. rufocanus. Close to the smelter, direct toxic effects of heavy metals may also reduce population densities. The results show that pollutants may change the relative proportions of microtine species.     

Osteopenia and osteoporosis can be predicted from Pap test

OBJECTIVE: To determine sensitivity and specificity of Pap tests for osteopenia and osteoporosis using bone mineral density (BMD) with dual x-ray absorptiometry (DXA) as the reference standard. STUDY DESIGN: DXA measurement was performed on 136 routine Pap smears. Results of DXA measurement were expressed in T-scores, indicating degree of deviation compared to a young adult population of same age and gender. Smears were grouped into atrophic and mature cell patterns. Using a stereologic analysis, mean areas of squamous cells, their nuclei and their cytoplasm were estimated. RESULTS: There was significant positive correlation between cell area and T-score (p < 0.001), as well as between cytoplasm area and T-score (p < 0.001). There was no significant relationship between nucleus area and T-score (p > 0.05). Mean T-scores of patients with atrophic cells were significantly lower than mean T-scores of patients with mature cell patterns (p < 0.001). The group including patients with atrophic or mature cells had a sensitivity of 61.4% and specificity of 86.4%, with positive predictive value of 95.9% in detecting patients with osteopenia or osteoporosis. CONCLUSION: Women with atrophic smear pattern are susceptible to osteopenia or osteoporosis; many cases could be detected with routine Pap test without additional costs.     

Role of the genetic component in osteopenic syndrome pathogenesis in children from regions with a polluted environment

Molecular genetic data and the results of an instrumental examination (ultrasonic densitometry) in 125 children from regions with anthropogenic pollution of the environment and 31 control group children from an area with an unpolluted environment have been analyzed. The molecular-genetic approach was used to study TaqI and ApaI polymorphic loci of the vitamin D3 receptor gene. Osteopenia and osteoporosis diagnosis frequency was 1.5 times higher in children from regions with a polluted environment. A decrease of bone mineral density was most common in children with tt and Tt genotypes (100 and 45%, respectively) and those with AA and Aa genotypes (83 and 42%, respectively). This is in agreement with published data on lower values of this parameter being associated with the ttAA genotype. Comprehensive assessment of instrumental and clinical laboratory parameters of bone density in carriers of certain allelic variants of the TaqI (rs731236) and ApaI (rs739837) polymorphic loci of the vitamin D3 receptor gene has been performed.