Calcium Bone Loss Research Articles

A Highly Flexible Piezoelectric Ultrasonic Sensor for Wearable Bone Density Testing.

Driven by the loss of bone calcium, the elderly are prone to osteoporosis, and regular routine checks on bone status are necessary, which mainly rely on bone testing equipment. Therefore, wearable real-time healthcare devices have become a research hotspot. Herein, we designed a high-performance flexible ultrasonic bone testing system using axial transmission technology based on quantitative ultrasound theory. First, a new rare-earth-element-doped PMN-PZT piezoelectric ceramic was synthesized using a solid-state reaction, and characterized by X-ray diffraction and SEM. Both a high piezoelectric coefficient d33 = 525 pC/N and electromechanical coupling factors of k33 = 0.77, kt = 0.58 and kp = 0.63 were achieved in 1%La/Sm-doped 0.17 PMN-0.47 PZ-0.36 PT ceramics. Combining a flexible PDMS substrate with an ultrasonic array, a flexible hardware circuit was designed which includes a pulse excitation module, ultrasound array module, amplification module, filter module, digital-to-analog conversion module and wireless transmission module, showing high power transfer efficiency and power intensity with values of 35% and 55.4 mW/cm2, respectively. Finally, the humerus, femur and fibula were examined by the flexible device attached to the skin, and the bone condition was displayed in real time on the mobile client, which indicates the potential clinical application of this device in the field of wearable healthcare.

Quasi-dendritic sulfonate-based organic small molecule for high-quality NIR-II bone-targeted imaging

The visualization of bone imaging in vivo is of great significance for the understanding of some bone-related diseases or physiological processes. Herein, a bone-targeted NIR-II small molecule (TTQF-SO3), which was modified with multiple sulfonate groups, was successfully fabricated for the second near-infrared (NIR-II) bone imaging. In vitro studies revealed that TTQF-SO3 showed high affinity for hydroxyapatite and excellent macrophage accumulation ability. In in vivo assays, TTQF-SO3 displayed high bone uptake ability and high NIR-II bone imaging quality, demonstrating the specific bone-targeting ability of the sulfonate-containing probe. In addition, the noninvasive NIR-II imaging detection in bone calcium loss was successfully verified in osteoporosis mice models. Moreover, the negative charge characteristic of TTQF-SO3 showed efficient lymphoid enrichment in living mice by intravenous injection. Overall, these warrant that our TTQF-SO3 is an optimal bone-targeted diagnostic agent for high-quality NIR-II imaging, highlighting its potential promise for clinical translation.Graphical

Topical application of the plant extract SDTL-E in ovariectomized rats: A potential new approach for treating osteoporosis.

Current osteoporosis medications have drawbacks of causing side effects and having slow onset, therefore developing osteoporosis drugs with faster onset and less side effects is essential. This study investigated the effects of the natural plant extract, SDTL-E, in ovariectomized (OVX)-induced osteoporosis rats. Rats were randomly assigned to sham operation control group (Control Group); OVX rat model group (Model Group) or OVX rat SDTL-E treatment group (SDTL-E Group). All groups underwent ovariectomy, but the Control Group did not have the ovaries removed. SDTL-E Group was treated with SDTL-E, Model and Control Groups were treated with vegetable oil, treatments were topically applied twice daily for 20 days. Results showed when compared with Model Group, SDTL-E Group significantly restored serum estradiol back to near Control Group level, serum ALP activity, serum and urinary calcium were significantly decreased, bone mechanics indicators increased and trabecular bone numbers slightly increased. These results demonstrated 20 days of SDTL-E topical treatment improved bone strength and trabecular bone structure in OVX-induced osteoporosis rats. The underlying mechanisms include restoring estradiol level, reducing bone turnover, net bone resorption, bone calcium loss, and calcium excretion through kidney. These findings suggest topical application of plant extract is a potential new approach with quick efficacy for treating osteoporosis.

Taphonomic bias in preservation and representativeness of skeletal samples (a case of Gonur Depe)

The topic of this article is theoretical and practical issues underlying the problems of representativeness of skeletal samples, as well as age and sex biases in preservation of skeletal remains, and the impact of these fac-tors on paleodemographic reconstructions. The impact of taphonomic bias in preservation on the qualitative and quantitative composition of skeletal sample is discussed on the materials from Gonur Depe — a Bronze Age proto-urban center in Southern Turkmenistan (2500–1500 BC, BMAC — Bactria-Margiana archaeological com-plex, also referred to as Oxus Civilization). The analyzed sample consists of skeletal remains of 500 individuals (215 non-adults, 115 adult males and 170 adult females) excavated between 2008 and 2015. Based on the type of preservation of skeletal remains, their completeness, as well as the preservation index (computed for each individual by dividing the number of long bones present by 14 — their maximum number per individual), three preservation classes were identified, of which class 1 corresponds to poor, and class 3 — to good state of preser-vation. Comparison of sex and age groups per each preservation class using сhi-square test demonstrates that in the Gonur Depe skeletal remains of infants (0–4 years old) and young adults (under 35 years of age) show the best state of preservation. Skeletons of elderly adults (over 35 years of age) have the worst state of preservation. There are no statistically significant differences between sexes in the degree of bone preservation. On the one hand, these results, contrary to theoretical expectations, testify against the existence of taphonomic biases in preservation of infant and female skeletons. On the other hand, the underrepresentation of elderly individuals in the studied collection is probably explained by a decrease in resistance to taphonomic processes due to the ac-celerated loss of bone calcium. It has been concluded that age and sex-related biases in the demographic struc-ture of prehistoric skeletal samples cannot be universally explained by the preservation factor. Misrepresentation in the percentage of different age and sex groups is a non-linear and a complicated process that requires consid-eration of different factors affecting the qualitative and quantitative composition of a particular skeletal sample. A detailed assessment of the taphonomic characteristics of a studied skeletal collection should be a mandatory step prior to its analysis by paleodemographic methods.

Vitamin K alleviates bone calcium loss caused by Salmonella Enteritidis through carboxylation of osteocalcin

BackgroundThe present study aimed at evaluating the effect of vitamin K (VK) supplementation on bone health of laying hens challenged by Salmonella Enteritidis.MethodsA total of 80 32-week-old double negative salmonella-free brown-egg laying hens were randomly assigned to 4 treatments with 20 replicates each (1 bird per replicate) according to a 2 × 2 factorial design with 2 dietary VK supplementation levels [0 mg/kg (VK0) vs 2 mg/kg VK (VK2) and 2 challenge treatments [Salmonella Enteritidis (SE) vs physiological saline solution (PS)]. During the last 3 days of week 43 of age, birds of both VK treatments were either orally challenged with 1.0 mL suspension of 109 cfu/mL S. Enteritidis daily or received the same volume of PS.ResultsThe laying rate, daily egg mass, tibia strength, CT, cOC and cOC/(cOC + ucOC) of VK2 treatment increased (P < 0.05) in contrast to VK0, however, the medullary area and ucOC of VK2 treatment decreased (P < 0.05) in contrast to VK0. Mortality, medullary area, serum Ca content of SE treatments increased (P < 0.05) in contrast to PS treatments. In both SE treatments, the decrease (P < 0.05) in birds’ tibia strength was associated with higher (P < 0.05) Ca levels in serum. There is an interaction (P < 0.05) between SE challenge and VK levels with regard to tibia strength and serum Ca levels. At week 42, serum CT was positively correlated with cOC (R = 0.99, P = 0.009); at week 44, tibia strength was positively correlated with BMD (R = 0.95, P = 0.045), but negatively correlated with medullary area (R = − 0.98, P = 0.018).ConclusionsVK (2 mg/kg) supplementation to diets of laying hens can enhance bone strength under challenge situations with Salmonella Enteritidis. Medullary area has proven to be a sensitive biomarker for bone calcium loss caused by SE infection.

Thomas H. Kunz

Thomas H. Kunz

Fortified tuna bone powder supplementation increases bone mineral density of lactating rats and their offspring.

Breastfeeding leads to bone calcium loss for milk production, resulting in progressive maternal osteopenia. Calcium supplement from natural sources has been postulated to be more beneficial to bone health than purified CaCO3 because natural sources also contain other nutrients such as certain amino acids that might enhance calcium metabolism. Herein, we examined the effect of calcium supplementation from tuna bone powder and CaCO3 on bones of dams and the offspring. Both forms of calcium supplement, i.e. tuna bone powder and CaCO3 , increased maternal bone mineral density (BMD). However, bone histomorphometry revealed that only tuna bone had beneficial effect on maternal bone microstructure, i.e. increased bone formation, decreased bone resorption and increased in bone volume. Regarding the mechanical properties, the decreased ultimate load in non-supplement lactating mothers was restored to the load seen in nulliparous animals by calcium supplementation. Moreover, both tuna bone and CaCO3 supplementation in mothers led to increased milk calcium concentration and consequently increased BMD in the growing offspring. Calcium supplement from tuna bone powder was effective in preventing maternal osteopenia. Tuna bone, which is a readily available fishing industrial waste, is a good alternative source of calcium supplement that increases BMD in both lactating mothers and the neonates. © 2017 Society of Chemical Industry.

Eurycoma longifolia as a potential alternative to testosterone for the treatment of osteoporosis: Exploring time-mannered proliferative, differentiative and morphogenic modulation in osteoblasts

Ethnopharmacological relevanceEurycoma longifolia (EL) has been well-studied traditionally as a chief ingredient of many polyherbal formulations for the management of male osteoporosis. It has also been well-recognised to protect against bone calcium loss in orchidectomised rats. Aim of the studyTo evaluate the effects of EL on the time-mannered sequential proliferative, differentiative, and morphogenic modulation in osteoblasts compared with testosterone. Materials and methodsCell proliferation was analysed using MTS assay and phase contrast microscopy. Osteogenic differentiation of MC3T3-E1 cells was assessed through a series of characteristic assays which include crystal violet staining, alkaline phosphatase (ALP) activity and Van Gieson staining. Taken together, the bone mineralization of extra cellular matrix (ECM) was estimated using alizarin red s (ARS) staining, von kossa staining, scanning electron microscopic (SEM) and energy dispersive x-ray (EDX) analysis. ResultsThe cell proliferation data clearly revealed the efficiency of EL particularly at a dose of 25µg/mL, in improving the growth of MC3T3-E1 cells compared with the untreated cells. Data also showed the prominence of EL in significantly promoting ALP activity throughout the entire duration of treatment compared with the testosterone-treated cells. The osteogenic differentiation potential of EL was further explored by analysing mineralization data which revealed that the calcified nodule formation (calcium deposition) and phosphate deposition was more pronounced in cells treated with 25µg/mL concentration of EL at various time points compared with the untreated and testosterone treated cells. The scanning electron microscopic (SEM) analysis also revealed highest globular masses of mineral deposits (identified as white colour crystals) in the ECM of cultured cells treated with 25µg/mL concentration of EL. ConclusionCompared to testosterone, greater potential of EL in promoting the proliferation and osteogenic differentiation of MC3T3-E1 cells provides an in vitro basis for the prevention of male osteoporosis. Thus, we anticipate that EL can be considered as an alternative approach to testosterone replacement therapy (TRT) for the treatment of male osteoporosis.

EURYCOMA LONGIFOLIA, A MALAYSIAN MEDICINAL HERB, SIGNIFICANTLY UPREGULATES PROLIFERATION AND DIFFERENTIATION IN PRE-OSTEOBLASTS (MC3T3-E1): AN IN VITRO MODEL

Objective: Eurycoma longifolia (EL), a well-recognized Malaysian medicinal herb, has gained widespread popularity due to its ability to protect against bone calcium loss in androgen-deficient osteoporosis. Nevertheless numerous animal studies have proved the bone protective effect of EL; however, the exact mechanism is not well-explained yet. Thus, the present study was aimed to explore the in vitro basis of bone protective effects of EL by using mouse pre-osteoblast cell line (MC3T3-E1).Methods: The cytotoxicity and proliferative potential of EL were evaluated by lactate dehydrogenase (LDH) and cell counting methods. Despite cell growth, the ability of EL to promote osteogenic differentiation of bone-forming cells was assessed by quantifying collagen (early differentiation marker) and calcium (late differentiation marker) in EL-treated bone forming cells.Results: Resulting data obtained from dose optimization study revealed that EL at 5 to 50 µg/ml concentration showed marked effects in significantly promoting cell growth in MC3T3-E1 cells. As such, resulting data also demonstrated the superior potential of EL in up regulating collagen synthesis and mineralization (calcium deposition) in MC3T3-E1 cells at 25 µg/ml, in comparison to untreated (negative control) and dihydrotestosterone (5α-DHT)-treated cells (positive control).Conclusion: These pronounced effects of EL on osteoblasts provide an in vitro basis for the bone protective potential of EL and thus can be considered as an alternative regimen for the treatment of androgen-deficient male osteoporosis.

Bone metabolism and renal stone risk during International Space Station missions

Bone loss and renal stone risk are longstanding concerns for astronauts. Bone resorption brought on by spaceflight elevates urinary calcium and the risk of renal stone formation. Loss of bone calcium leads to concerns about fracture risk and increased long-term risk of osteoporosis. Bone metabolism involves many factors and is interconnected with muscle metabolism and diet. We report here bone biochemistry and renal stone risk data from astronauts on 4- to 6-month International Space Station missions. All had access to a type of resistive exercise countermeasure hardware, either the Advanced Resistance Exercise Device (ARED) or the Interim Resistance Exercise Device (iRED). A subset of the ARED group also tested the bisphosphonate alendronate as a potential anti-resorptive countermeasure (Bis+ARED). While some of the basic bone marker data have been published, we provide here a more comprehensive evaluation of bone biochemistry with a larger group of astronauts. Regardless of exercise, the risk of renal stone formation increased during spaceflight. A key factor in this increase was urine volume, which was lower during flight in all groups at all time points. Thus, the easiest way to mitigate renal stone risk is to increase fluid consumption. ARED use increased bone formation without changing bone resorption, and mitigated a drop in parathyroid hormone in iRED astronauts. Sclerostin, an osteocyte-derived negative regulator of bone formation, increased 10–15% in both groups of astronauts who used the ARED (p<0.06). IGF-1, which regulates bone growth and formation, increased during flight in all 3 groups (p<0.001). Our results are consistent with the growing body of literature showing that the hyper-resorptive state of bone that is brought on by spaceflight can be countered pharmacologically or mitigated through an exercise-induced increase in bone formation, with nutritional support. Key questions remain about the effect of exercise-induced alterations in bone metabolism on bone strength and fracture risk.

Calcium kinetics during bed rest with artificial gravity and exercise countermeasures.

We assessed the potential for countermeasures to lessen the loss of bone calcium during bed rest. Subjects ingested less calcium during bed rest, and with artificial gravity, they also absorbed less calcium. With exercise, they excreted less calcium. To retain bone during bed rest, calcium intake needs to be maintained. This study aims to assess the potential for artificial gravity (AG) and exercise (EX) to mitigate loss of bone calcium during space flight. We performed two studies: (1) a 21-day bed rest (BR) study with subjects receiving 1h/day AG (n = 8) or no AG (n = 7) and (2) a 28-day BR study with 1h/day resistance EX (n = 10) or no EX (n = 3). In both studies, stable isotopes of Ca were administered orally and intravenously, at baseline and after 10days of BR, and blood, urine, and feces were sampled for up to 14days post dosing. Tracers were measured using thermal ionization mass spectrometry. Data were analyzed by compartmental modeling. Less Ca was absorbed during BR, resulting in lower Ca balance in BR+AG (-6.04 ± 3.38mmol/day, P = 0.023). However, Ca balance did not change with BR+EX, even though absorbed Ca decreased and urinary Ca excretion increased, because endogenous excretion decreased, and there was a trend for increased bone deposition (P = 0.06). Urinary N-telopeptide excretion increased in controls during BR, but not in the EX group. Markers of bone formation were not different between treatment groups for either study. Ca intake decreased during BR (by 5.4mmol/day in the AG study and 2.8mmol/day in the EX study), resulting in lower absorbed Ca. During BR (or space flight), Ca intake needs to be maintained or even increased with countermeasures such as exercise, to enable maintenance of bone Ca.

Eurycoma longifolia upregulates osteoprotegerin gene expression in androgen- deficient osteoporosis rat model

BackgroundEurycoma longifolia (EL) has been shown recently to protect against bone calcium loss in orchidectomised rats, the model for androgen-deficient osteoporosis. The mechanism behind this is unclear but it may be related to its ability to elevate testosterone levels or it may directly affect bone remodeling. The aim of this study is to determine the mechanism involved by investigating the effects of EL extract on serum testosterone levels, bone biomarkers, biomechanical strength and gene expression of Receptor Activator of Nuclear Factor kappa-B ligand (RANKL), Osteoprotegerin (OPG) and Macrophage-Colony Stimulating Factor (MCSF) in orchidectomised rats.MethodsThirty-two male Sprague–Dawley rats were divided into: Sham-operated group (SHAM); orchidectomised-control group (ORX); orchidectomised and given 15 mg/kg EL extract (ORX + EL) and orchidectomised and given 8 mg/kg testosterone (ORX + T). The rats were treated for 6 weeks. The serum levels of testosterone, osteocalcin and C-terminal telopeptide of type I collagen (CTX) were measured using the ELISA technique. The femoral bones were subjected to biomechanical testing. The tibial bone gene expressions of RANKL, OPG and MCSF were measured using the branch DNA technique.ResultsThe post-treatment level of testosterone was found to be significantly reduced by orchiectomy (p < 0.05). Both ORX + EL and ORX + T groups have significantly higher post-treatment testosterone levels compared to their pre-treatment levels (p < 0.05). The bone resorption marker (CTx) was elevated after orchiectomy but was suppressed after treatment in the ORX + EL and ORX + T groups (p < 0.05). There was no significant finding for the femoral biomechanical parameters. The tibial OPG gene expression in the ORX group was significantly lower compared to the SHAM and ORX + EL groups (p < 0.05).ConclusionSupplementation with EL extract elevated the testosterone levels, reduced the bone resorption marker and upregulated OPG gene expression of the orchidectomised rats. These actions may be responsible for the protective effects of EL extract against bone resorption due to androgen deficiency.

Effects ofEurycoma longifoliaon Testosterone Level and Bone Structure in an Aged Orchidectomised Rat Model

Testosterone replacement is the choice of treatment in androgen-deficient osteoporosis. However, long-term use of testosterone is potentially carcinogenic. Eurycoma longifolia (EL) has been reported to enhance testosterone level and prevent bone calcium loss but there is a paucity of research regarding its effect on the bone structural parameters. This study was conducted to explore the bone structural changes following EL treatment in normal and androgen-deficient osteoporosis rat model. Thirty-six male Sprague-Dawley rats aged 12 months were divided into normal control, normal rat supplemented with EL, sham-operated, orchidectomised-control, orchidectomised with testosterone replacement, and orchidectomised with EL supplementation groups. Testosterone serum was measured both before and after the completion of the treatment. After 6 weeks of the treatment, the femora were processed for bone histomorphometry. Testosterone replacement was able to raise the testosterone level and restore the bone volume of orchidectomised rats. EL supplementation failed to emulate both these testosterone actions. The inability of EL to do so may be related to the absence of testes in the androgen deficient osteoporosis model for EL to stimulate testosterone production.

The effects of Labisia pumila var. alata on bone markers and bone calcium in a rat model of post-menopausal osteoporosis

Postmenopausal osteoporosis is mainly treated with estrogen replacement therapy (ERT). However, ERT causes side effects, mainly breast cancer, uterine cancer and thromboembolic problems. Labisia pumila var. arata (LPva), a herb with phytoestrogenic effects has the potential to be used as an alternative agent to ERT. This study was conducted to determine the effects of LPva on bone biochemical markers and bone calcium content in ovariectomised rats. Thirty two Wistar rats were divided into 4 groups, with 8 rats in each group. The first group was sham operated (Sham), the second group was ovariectomised (OVX), the third (LPva) and fourth group (ERT) were also ovariectomised and given LPva 17.5 mg/kg and Premarin(®) 64.5 μg/kg, respectively. Blood samples were taken before and after treatment to measure osteocalcin and C-terminal telopeptide of type 1 collagen levels using ELISA while the fifth lumbar bone samples were taken to measure bone calcium content using the Atomic Absorption Spectrophotometer (AAS). The osteocalcin levels were significantly higher in both the LPva and ERT groups compared to the OVX group. The CTX levels were significantly lower in both the LPva and ERT groups compared to the OVX group. However, only the ERT group had significantly higher bone calcium level compared to the OVX group. The supplementation of 17.5 mg/kg of LPva to ovariectomised rats for 8 weeks was able to prevent the changes in bone biochemical markers but failed to prevent the bone calcium loss induced by ovariectomy.

Loss of Bone Calcium in Exposure to 50 Hz Magnetic Fields

This study investigates the effect of whole body exposure to magnetic fields on the calcium level of blood and bone in a trial to avoid the liability of osteoporosis, fractures, and delayed union of fractures after exposure to magnetic fields present everywhere in the environment. The procedures of the study included analysis for calcium level in both bone and blood. The procedures were performed on 50 Guinea pigs equally divided into 5 groups. Groups A, B, C, and D were exposed to 50 Hz, 0.2 mT magnetic field for 30 d. Group E animals were the control. Group A was sacrificed immediately after exposure; Group B was left away from the field for 15 d for spontaneous repair; Group C received the drug Centrum dissolved in drinking water for 15 d after exposure to the magnetic field; and Group D received centrum in drinking water during the period of exposure (30 d). After sacrificing all animals, the calcium level in both bone and blood was evaluated. Values of blood analysis revealed significant increase in the blood calcium level in exposed animals compared with the control group (P < 0.002) with excess in Group A. This indicated that the calcium left the bone to the blood. Values of the bone analysis revealed significant decrease in bone calcium concentration level in Group A compared with the control group and improvement in the bone condition in Groups C and D, indicating the role of trace element after the exposure period as a compensatory agent of magnetic field damage and its role during the exposure period as a radio-protecting agent.

Effects of long-duration space flight on calcium metabolism: Review of human studies from Skylab to the present

One of the major effects of prolonged weightlessness seen in long-duration space flights has been an extended loss of bone from the skeleton. The principal characteristics of this loss were shown in the metabolic studies carried out on the Skylab flights of 1, 2 and 3 months in 1973 and 1974. These studies now provide the background for a comprehensive review of the considerable number of subsequent calcium studies in humans during space flights from that time until the present. Because of the close similarities in pattern and degree between space flight and bed rest in effects on calcium metabolism, relevant long-term human bed rest studies have been included. An analysis is presented of the bone calcium loss data with respect to degree, duration and significance, as well as relative failure of reversibility or recovery following flights. Possible mechanisms of bone loss are discussed: the physiological condition of disuse atrophy, increase in bone resorption, decrease (later and lesser) in bone formation, decrease in intestinal calcium absorption, increase in glucocorticoids, along with the threat of urinary tract stone formation and proposed countermeasures. Considerable future research is needed, particularly on mechanisms of bone loss and on countermeasures, to be carried out on the International Space Station and via bed rest studies, before a mission to and return from Mars is undertaken.

Nephrocalcinosis and hyperlipidemia in rats fed a cholesterol- and fat-rich diet: association with hyperoxaluria, altered kidney and bone minerals, and renal tissue phospholipid-calcium interaction.

To determine whether an "atherogenic" diet (excess of cholesterol and neutral fat) induces pathological calcification in various organs, including the kidney, and abnormal oxalate metabolism, 24 male Sprague-Dawley rats were fed either normal lab chow (controls, n = 12) or the cholesterol- and fat-rich experimental diet (CH-F, n = 12) for 111 +/- 3 days. CH-F rats developed dyslipidemia [high blood levels of triglycerides, total, low-density lipoprotein (LDL)-, very low-density lipoprotein (VLDL)-, high-density lipoprotein (HDL)-bound cholesterol, total phospholipids], elevated serum total alkaline phosphatase and lactate dehydrogenase (LDH) levels, in the absence of changes in overall renal function, extracellular mineral homeostasis [serum protein-corrected total calcium, magnesium, parathyroid hormone (PTH), 1,25-dihydroxyvitamin D (1,25(OH)2D)], plasma glycolate and oxalate levels. There was a redistribution of bone calcium and enhanced exchange of this within the extraosseous space, which was accompanied by significant bone calcium loss, but normal bone histomorphometry. Liver oxalate levels, if expressed per unit of defatted (DF) dry liver, were three times higher than in the controls. Urinary glycolate, oxalate, calcium and total protein excretion levels were elevated, the latter showing an excess of proteins > 100 kD and a deficit of proteins > 30-50 kD. Urinary calcium oxalate supersaturation was increased, and calcium phosphate supersaturation was unchanged. There were dramatically increased (by number, circumference, and area) renal calcium phosphate calcifications in the cortico-medullary region, but calcium oxalate deposits were not detectable. Electron microscopy (EM) and elemental analysis revealed intratubular calcium phosphate, apparently needle-like hydroxyapatite. Immunohistochemistry of renal tissue calcifications revealed co-localization of phospholipids and calcium phosphate. It is concluded that rats fed the CH-F diet exhibited: (1) a spectrum of metabolic abnormalities, the more prominent being dyslipidemia, hyperoxaluria, hypercalciuria, dysproteinuria, loss of bone calcium, and calcium phosphate nephrocalcinosis (NC); and (2) an interaction between calcium phosphate and phospholipids at the kidney level. The biological significance of these findings for the etiology of idiopathic calcium urolithiasis in humans is uncertain, but the presented animal model may be helpful when designing clinical studies.

Clinical review 108: The molecular and neuroanatomical basis for estrogen effects in the central nervous system.

With increasing life expectancy during the 20th century, women are likely to live a substantial part of their lives in a state of estrogen deficiency. Hot flushes are for many women the most dramatic and noticeable consequence of loss of ovarian hormones. Loss of bone calcium and osteoporosis, developing much more gradually, is another consequence that has led many women to take estrogen replacement therapy (ERT) at the menopause. Likewise, the loss of protection of the coronary arteries, leading postmenopausal women to increased risk for cardiovascular disease, is another result of estrogen deficiency that has reinforced the value of ERT. Yet, it is only quite recently that medical science has recognized that the brain is one of the organs of the body that suffers from the loss of this circulating hormone. This has happened despite studies over more than 30 yr indicating that estrogens target the brain of experimental animals (for summary, see Ref. 1). However, most of the animal studies have focused on estrogen actions on the hypothalamus affecting ovulation and reproductive behavior, and only recently has it become apparent that estrogens exert many actions outside of the reproductive function, including actions on brain areas that are important for learning and memory, emotions and affective state, as well as motor coordination and pain sensitivity. Indeed, some women experience at surgical or natural menopause difficulties in remembering names and other information important for daily life as well as deficits in fine motor coordination and reaction times and feelings of depression and anxiety (2). These effects reflect the actions of estrogens on a large number of brain areas outside of the hypothalamus. The problem in these brain regions has been to recognize the receptors and mechanisms by which estrogens produce their effects. This brief review will focus on two aspects: first, the cellular and molecular mechanisms by which estrogens produce their diverse effects on the brain; and second, the brain regions and cell types in which estrogens produce their effects, emphasizing new knowledge regarding estrogen actions outside of the hypothalamus and pituitary gland. Finally, a brief discussion will summarize the potential clinical applications of this information, particularly in relation to cognitive function and dementia.

Pamidronate [(3-amino-1-hydroxypropylidene)-1,1-bisphosphonate] prevents bone calcium loss during the first 3 months after renal transplantation

Pamidronate [(3-amino-1-hydroxypropylidene)-1,1-bisphosphonate] prevents bone calcium loss during the first 3 months after renal transplantation

Hypercalciuria in a new rat model of hyperprolactinemia

Hypercalciuria has been reported in rats with mild hyperprolactinemia due to implantation of anterior pituitary glands under the kidney capsule and in rats bearing transplantable tumors that secrete large amounts of prolactin (PRL) and growth hormone (GH). We studied Buffalo rats implanted subcutaneously with the new MMQ pituitary tumor line that secretes only PRL. Urinary calcium excretion increased as the tumors grew. Three weeks after tumor implantation in female rats, the urinary calcium excretion was 1.102 ± 0.092 mg 100 g body weight (BW) · 24 hours compared with controls, 0.296 ± 0.079, P < .0005. Male tumor-bearing rats also had increased urinary calcium excretion compared with male controls. In tumor-bearing rats the urinary calcium excretion factored for urinary sodium excretion, dietary calcium intake, or urinary creatinine excretion was elevated. Urinary calcium excretion was correlated with serum PRL levels and with estimated tumor volume. Serum calcium, immunoassayable parathyroid hormone, and urinary cyclic adenosine monophosphate (cAMP) excretion were normal in the tumor-bearing rats. There was some evidence of loss of bone calcium in rats bearing the MMQ tumor, and serum levels of calcitonin were decreased. These results are similar to those found in anterior pituitary-grafted hypercalciuric rats. It is unlikely that parathyroid hormone (PTH) abnormalities are responsible for the hypercalciuria in the MMQ-bearing rats. The pituitary gland may have an effect on the distal renal tubule to decrease calcium reabsorption.