Consumer behavior and exposure to parabens, bisphenols, triclosan, dichlorophenols, and benzophenone-3: Results from a crowdsourced biomonitoring study.

Nearly all Americans have detectable concentrations of endocrine disrupting chemicals from consumer products in their bodies, and expert panels recommend reducing exposures. To inform exposure reduction, we investigated whether consumers who are trying to avoid certain chemicals in consumer products have lower exposures than those who are not. We also aimed to make exposure biomonitoring more widely available. We enrolled 726 participants in a crowdsourced biomonitoring study. We targeted phenolic compounds-specifically parabens, bisphenol A (BPA) and analogs bisphenol F (BPF) and bisphenol S (BPS), the UV filter benzophenone-3, the anti-microbial triclosan, 2,4-dichlorophenol, and 2,5-dichlorophenol-and collected survey data on consumer products, cleaning habits, and efforts to avoid related chemicals. We investigated associations between 68 self-reported exposure behaviors and urine concentrations of ten chemicals, and evaluated whether associations were modified by intention to avoid exposures. A large majority (87%) of participants reported taking steps to limit exposure to specific chemicals, and, overall, participants achieved lower concentrations than the general U.S. population for parabens, BPA, triclosan, and benzophenone-3 but not BPF and BPS. Participants who reported avoiding all four ingredient groups-parabens, triclosan, bisphenols, and fragrances-were twice as likely as others to be in the lowest quartile of cumulative exposure. Avoiding certain products and reading ingredient labels to avoid chemicals was most effective for parabens, triclosan, and benzophenone-3. Avoiding BPA was not effective for reducing bisphenol exposures. Avoiding certain chemicals in products was generally associated with reduced exposure for chemicals listed on labels. Greater ingredient transparency will help consumers who read labels to reduce their exposure to a wider range of potentially harmful chemicals. In order to more equitably address public health, labeling policies should be complemented by regulations that exclude harmful chemicals from consumer products.

Perceived Risks, Benefits, and Interest in Participating in Environmental Health Studies That Share Personal Exposure Data: A U.S. Survey of Prospective Participants.

Little is known about the willingness of prospective study participants to share environmental health data. To fill this gap, we conducted a hypothetical vignette survey among 1,575 women who have volunteered to be contacted about breast cancer studies. Eighty-three percent were interested in participating in the environmental studies, with little difference whether data were restricted to the research team, shared with approved researchers, or publicly accessible. However, participants somewhat preferred controlled access for children's data. Respondents were more interested in studies with environmental rather than biological samples and more interested when researchers would return personal results, a practice of increasing importance. They were more reluctant to share location or to participate if studies involved electronic medical records. Many expressed concerns about privacy, particularly security breaches, but reidentification risks were mentioned infrequently, indicating that this topic should be discussed during informed consent.

Wrangling environmental exposure data: guidance for getting the best information from your laboratory measurements.

BACKGROUND: Environmental health and exposure researchers can improve the quality and interpretation of their chemical measurement data, avoid spurious results, and improve analytical protocols for new chemicals by closely examining lab and field quality control (QC) data. Reporting QC data along with chemical measurements in biological and environmental samples allows readers to evaluate data quality and appropriate uses of the data (e.g., for comparison to other exposure studies, association with health outcomes, use in regulatory decision-making). However many studies do not adequately describe or interpret QC assessments in publications, leaving readers uncertain about the level of confidence in the reported data. One potential barrier to both QC implementation and reporting is that guidance on how to integrate and interpret QC assessments is often fragmented and difficult to find, with no centralized repository or summary. In addition, existing documents are typically written for regulatory scientists rather than environmental health researchers, who may have little or no experience in analytical chemistry. OBJECTIVES: We discuss approaches for implementing quality assurance/quality control (QA/QC) in environmental exposure measurement projects and describe our process for interpreting QC results and drawing conclusions about data validity. DISCUSSION: Our methods build upon existing guidance and years of practical experience collecting exposure data and analyzing it in collaboration with contract and university laboratories, as well as the Centers for Disease Control and Prevention. With real examples from our data, we demonstrate problems that would not have come to light had we not engaged with our QC data and incorporated field QC samples in our study design. Our approach focuses on descriptive analyses and data visualizations that have been compatible with diverse exposure studies with sample sizes ranging from tens to hundreds of samples. Future work could incorporate additional statistically grounded methods for larger datasets with more QC samples. CONCLUSIONS: This guidance, along with example table shells, graphics, and some sample R code, provides a useful set of tools for getting the best information from valuable environmental exposure datasets and enabling valid comparison and synthesis of exposure data across studies.

Passive indoor air sampling for consumer product chemicals: a field evaluation study.

Innovative exposure measurement methods are needed for large environmental health studies, particularly for semivolatile organic compounds (SVOCs). Active air sampling methods are costly to implement, but passive air sampling presents a viable method. To expand and improve the use of passive air samplers (PAS) for indoor SVOC monitoring, we designed a unique, compact sampler using commercially available polyurethane foam (PUF) disks housed within durable, easy-to-setup, low-profile enclosures. We evaluated the new design using co-located active air samplers (AAS) and analyzed for SVOCs. Most of the targeted SVOCs found using active sampling (27 of 33) were also detected using passive sampling. We found good agreement (R2 = 0.88) between active and passive sampling methods for characterizing the relative abundance of each chemical, and the measured active sampler concentrations and passive sampler masses were significantly positively correlated for 14 of 21 chemicals, for which correlations could be estimated. We found that measurements of many SVOCs originating from consumer products and typically found in the gas-phase (log KOA < 10) can be reliably ranked-and thus appropriate for epidemiological studies-using this PAS design. These SVOCs include diethyl phthalate, AHTN, HHCB, tris(2-chloroethyl) phosphate, dibutyl phthalate, and tris(1-chloro-2-propyl) phosphate, as well as methyl paraben, benzophenone, and benzophenone-3, which have not previously been measured by passive sampling. This PAS can be used in epidemiological studies involving consumer product chemicals and complements other novel exposure tools.

Environmental chemicals and breast cancer: An updated review of epidemiological literature informed by biological mechanisms.

BACKGROUND: Many common environmental chemicals are mammary gland carcinogens in animal studies, activate relevant hormonal pathways, or enhance mammary gland susceptibility to carcinogenesis. Breast cancer's long latency and multifactorial etiology make evaluation of these chemicals in humans challenging. OBJECTIVE: For chemicals previously identified as mammary gland toxicants, we evaluated epidemiologic studies published since our 2007 review. We assessed whether study designs captured relevant exposures and disease features suggested by toxicological and biological evidence of genotoxicity, endocrine disruption, tumor promotion, or disruption of mammary gland development. METHODS: We systematically searched the PubMed database for articles with breast cancer outcomes published in 2006-2016 using terms for 134 environmental chemicals, sources, or biomarkers of exposure. We critically reviewed the articles. RESULTS: We identified 158 articles. Consistent with experimental evidence, a few key studies suggested higher risk for exposures during breast development to dichlorodiphenyltrichloroethane (DDT), dioxins, perfluorooctane-sulfonamide (PFOSA), and air pollution (risk estimates ranged from 2.14 to 5.0), and for occupational exposure to solvents and other mammary carcinogens, such as gasoline components (risk estimates ranged from 1.42 to 3.31). Notably, one 50-year cohort study captured exposure to DDT during several critical windows for breast development (in utero, adolescence, pregnancy) and when this chemical was still in use. Most other studies did not assess exposure during a biologically relevant window or specify the timing of exposure. Few studies considered genetic variation, but the Long Island Breast Cancer Study Project reported higher breast cancer risk for polycyclic aromatic hydrocarbons (PAHs) in women with certain genetic variations, especially in DNA repair genes. CONCLUSIONS: New studies that targeted toxicologically relevant chemicals and captured biological hypotheses about genetic variants or windows of breast susceptibility added to evidence of links between environmental chemicals and breast cancer. However, many biologically relevant chemicals, including current-use consumer product chemicals, have not been adequately studied in humans. Studies are challenged to reconstruct exposures that occurred decades before diagnosis or access biological samples stored that long. Other problems include measuring rapidly metabolized chemicals and evaluating exposure to mixtures.

Chemical exposures in recently renovated low-income housing: Influence of building materials and occupant activities.

Health disparities in low-income communities may be linked to residential exposures to chemicals infiltrating from the outdoors and characteristics of and sources in the home. Indoor sources comprise those introduced by the occupant as well as releases from building materials. To examine the impact of renovation on indoor pollutants levels and to classify chemicals by predominant indoor sources, we collected indoor air and surface wipes from newly renovated "green" low-income housing units in Boston before and after occupancy. We targeted nearly 100 semivolatile organic compounds (SVOCs) and volatile organic compounds (VOCs), including phthalates, flame retardants, fragrance chemicals, pesticides, antimicrobials, petroleum chemicals, chlorinated solvents, and formaldehyde, as well as particulate matter. All homes had indoor air concentrations that exceeded available risk-based screening levels for at least one chemical. We categorized chemicals as primarily influenced by the occupant or as having building-related sources. While building-related chemicals observed in this study may be specific to the particular housing development, occupant-related findings might be generalizable to similar communities. Among 58 detected chemicals, we distinguished 25 as primarily occupant-related, including fragrance chemicals 6-acetyl-1,1,2,4,4,7-hexamethyltetralin (AHTN) and 1,3,4,6,7,8-hexahydro-4,6,6,7,8,8-hexamethylcyclopenta[g]-2-benzopyran (HHCB). The pre- to post-occupancy patterns of the remaining chemicals suggested important contributions from building materials for some, including dibutyl phthalate and xylene, whereas others, such as diethyl phthalate and formaldehyde, appeared to have both building and occupant sources. Chemical classification by source informs multi-level exposure reduction strategies in low-income housing.

New insights into the effects of primary hyperparathyroidism on the cortical and trabecular compartments of bone.

In primary hyperparathyroidism (PHPT), protracted elevation of serum parathyroid hormone (PTH) is held to be associated with cortical, but not trabecular, bone loss. However, an alternative explanation for the apparent preservation of trabecular bone is fragmentation of the cortex by intracortical remodeling. The cortical fragments resemble trabeculae and so may be erroneously included in the quantification of 'trabecular' bone density. To test this hypothesis, we compared bone microarchitecture in 43 patients with untreated PHPT (mean 62.9 years, range 31-84) with 47 healthy age-matched controls and 25 patients with surgically treated PHPT (63.6 years, 30-82). Images of the distal radius and tibia were acquired using high-resolution peripheral quantitative CT and analysed using StrAx1.0, a new software program that quantifies bone morphology in-vivo. Results were expressed as the mean number of standardized deviations (SD) from the age-specific mean (Z scores, mean±SEM). In subjects with PHPT, total tibial cortical area was reduced -0.26±0.08 SD; p=0.002). Cortical volumetric bone mineral density (vBMD) was reduced (-0.29±0.06 SD; p<0.001) due to higher cortical porosity (0.32±0.06 SD; p<0.001) and lower tissue mineralization density (-0.21±0.06 SD; p=0.002). Medullary area was increased (0.26±0.08 SD; p=0.002) and trabecular vBMD was reduced (-0.14±0.04 SD; p<0.001). In subjects who underwent successful parathyroidectomy, cortical area (-0.18±0.10 SD; NS) and medullary area (0.18±0.10 SD; NS) did not differ from controls. Cortical vBMD was reduced (-0.15±0.05 SD; p=0.003) due to high porosity (0.15±0.05 SD; p=0.006), values numerically lower than in untreated PHPT. Tissue mineralization density (-0.26±0.04 SD; p<0.001) and trabecular vBMD were reduced (-0.16±0.04 SD, p<0.001). The results were similar in the distal radius. In PHPT, chronically elevated endogenous PTH does not spare trabecular bone; it causes bone loss and microarchitectural deterioration in both cortical and trabecular compartments of bone.

Trabecular bone score (TBS)--a novel method to evaluate bone microarchitectural texture in patients with primary hyperparathyroidism.

CONTEXT: In the milder form of primary hyperparathyroidism (PHPT), cancellous bone, represented by areal bone mineral density at the lumbar spine by dual-energy x-ray absorptiometry (DXA), is preserved. This finding is in contrast to high-resolution peripheral quantitative computed tomography (HRpQCT) results of abnormal trabecular microstructure and epidemiological evidence for increased overall fracture risk in PHPT. Because DXA does not directly measure trabecular bone and HRpQCT is not widely available, we used trabecular bone score (TBS), a novel gray-level textural analysis applied to spine DXA images, to estimate indirectly trabecular microarchitecture. OBJECTIVE: The purpose of this study was to assess TBS from spine DXA images in relation to HRpQCT indices and bone stiffness in radius and tibia in PHPT. DESIGN AND SETTING: This was a cross-sectional study conducted in a referral center. PATIENTS: Participants were 22 postmenopausal women with PHPT. MAIN OUTCOME MEASURES: Outcomes measured were areal bone mineral density by DXA, TBS indices derived from DXA images, HRpQCT standard measures, and bone stiffness assessed by finite element analysis at distal radius and tibia. RESULTS: TBS in PHPT was low at 1.24, representing abnormal trabecular microstructure (normal ≥1.35). TBS was correlated with whole bone stiffness and all HRpQCT indices, except for trabecular thickness and trabecular stiffness at the radius. At the tibia, correlations were observed between TBS and volumetric densities, cortical thickness, trabecular bone volume, and whole bone stiffness. TBS correlated with all indices of trabecular microarchitecture, except trabecular thickness, after adjustment for body weight. CONCLUSION: TBS, a measurement technology readily available by DXA, shows promise in the clinical assessment of trabecular microstructure in PHPT.

Primary hyperparathyroidism is associated with abnormal cortical and trabecular microstructure and reduced bone stiffness in postmenopausal women.

Typically, in the milder form of primary hyperparathyroidism (PHPT), now seen in most countries, bone density by dual-energy X-ray absorptiometry (DXA) and detailed analyses of iliac crest bone biopsies by histomorphometry and micro-computed tomography (µCT) show detrimental effects in cortical bone, whereas the trabecular site (lumbar spine by DXA) and the trabecular compartment (by bone biopsy) appear to be relatively well preserved. Despite these findings, fracture risk at both vertebral and nonvertebral sites is increased in PHPT. Emerging technologies, such as high-resolution peripheral quantitative computed tomography (HRpQCT), may provide additional insight into microstructural features at sites such as the forearm and tibia that have heretofore not been easily accessible. Using HRpQCT, we determined cortical and trabecular microstructure at the radius and tibia in 51 postmenopausal women with PHPT and 120 controls. Individual trabecula segmentation (ITS) and micro-finite element (µFE) analyses of the HRpQCT images were also performed to further understand how the abnormalities seen by HRpQCT might translate into effects on bone strength. Women with PHPT showed, at both sites, decreased volumetric densities at trabecular and cortical compartments, thinner cortices, and more widely spaced and heterogeneously distributed trabeculae. At the radius, trabeculae were thinner and fewer in PHPT. The radius was affected to a greater extent in the trabecular compartment than the tibia. ITS analyses revealed, at both sites, that plate-like trabeculae were depleted, with a resultant reduction in the plate/rod ratio. Microarchitectural abnormalities were evident by decreased plate-rod and plate-plate junctions at the radius and tibia, and rod-rod junctions at the radius. These trabecular and cortical abnormalities resulted in decreased whole-bone stiffness and trabecular stiffness. These results provide evidence that in PHPT, microstructural abnormalities are pervasive and not limited to the cortical compartment, which may help to account for increased global fracture risk in PHPT.

Effect of renal function on skeletal health in primary hyperparathyroidism.

CONTEXT: Current guidelines recommend parathyroidectomy in patients with primary hyperparathyroidism (PHPT) who have an estimated glomerular filtration rate (eGFR) less than 60 ml/min per 1.73 m(2). It is unclear, however, whether values below this threshold of renal impairment affect bone and mineral metabolism in PHPT. OBJECTIVE: The purpose of this study was to assess the effect of renal function on skeletal health in PHPT. DESIGN: This is a retrospective analysis of PHPT patients with (eGFR < 60 ml/min per 1.73 m(2)) and without chronic kidney disease (CKD) from our previously described PHPT cohort recruited from 1984 to 1991. SETTING: The study was conducted in a university hospital metabolic bone unit. PARTICIPANTS: One hundred thirty-eight women and men with PHPT were studied. OUTCOME MEASURES: We assessed bone mineral density (BMD) by dual-energy x-ray absorptiometry; quantitative histomorphometric indices from transiliac bone biopsies; and biochemical markers of mineral metabolism. RESULTS: Although there was no difference in serum or urinary calcium or PTH level, calcitriol levels were lower and phosphate levels higher in patients with CKD. BMD adjusted for weight did not differ at any site between groups. Histomorphometric analysis (n = 30 of 138) revealed a 45% greater eroded surface in those with CKD (P = 0.02). Eroded surface negatively correlated with eGFR (r = -0.46, P = 0.02) and phosphate (r = -0.48, P = 0.02) and positively correlated with serum calcium level (r = 0.51, P = 0.009) but not with PTH, alkaline phosphatase, vitamin D metabolites, or urinary calcium excretion. CONCLUSION: Although cardinal biochemical indices (such as calcium and PTH) and BMD do not differ in PHPT patients with an eGFR below 60 ml/min per 1.73 m(2), these patients have higher phosphate and histomorphometric evidence of altered bone remodeling compared with those without CKD.

Differences in bone microarchitecture between postmenopausal Chinese-American and white women.

Chinese-American women have lower rates of hip and forearm fracture than white women despite lower areal bone density (aBMD) by dual X-ray absorptiometry (DXA). We recently reported higher trabecular (D(trab) ) and cortical (D(comp) ) bone density as well as greater trabecular (Tb.Th) and cortical thickness (C.Th) but smaller bone area (CSA), as measured by high-resolution peripheral quantitative computed tomography (HR-pQCT), in premenopausal Chinese-American compared with white women. These findings may help to account for the lower fracture rate among Chinese-American women but were limited to measurements in premenopausal women. This study was designed to extend these investigations to postmenopausal Chinese-American (n = 29) and white (n = 68) women. Radius CSA was 10% smaller in the Chinese-American versus the white group (p = .008), whereas their C.Th and D(comp) values were 18% and 6% greater (p < .001 for both). Tibial HR-pQCT results for cortical bone were similar to the radius, but Tb.Th was 11% greater in Chinese-American versus white women (p = .007). Tibial trabecular number and spacing were 17% lower and 20% greater, respectively, in Chinese-American women (p < .0001 for both). There were no differences in trabecular or whole-bone stiffness estimated by microstructural finite-element analysis, but Chinese-American women had a greater percentage of load carried by the cortical bone compartment at the distal radius and tibia. There was no difference in load distribution at the proximal radius or tibia. Whole-bone finite-element analysis may indicate that the thicker, more dense cortical bone and thicker trabeculae in postmenopausal Chinese-American women compensate for fewer trabeculae and smaller bone size.

Better skeletal microstructure confers greater mechanical advantages in Chinese-American women versus white women.

Despite lower areal bone mineral density (aBMD), Chinese-American women have fewer fractures than white women. We hypothesized that better skeletal microstructure in Chinese-American women in part could account for this paradox. Individual trabecula segmentation (ITS), a novel image-analysis technique, and micro-finite-element analysis (µFEA) were applied to high-resolution peripheral quantitative computed tomography (HR-pQCT) images to determine bone microarchitecture and strength in premenopausal Chinese-American and white women. Chinese-American women had 95% and 80% higher plate bone volume fraction at the distal radius and tibia, respectively, as well as 20% and 18% higher plate number density compared with white women (p < .001). With similar rodlike characteristics, the plate-to-rod ratio was twice as high in the Chinese-American than in white trabecular bone (p < .001). Plate-rod junction density, a parameter indicating trabecular network connections, was 37% and 29% greater at the distal radius and tibia, respectively, in Chinese-American women (p < .002). Moreover, the orientation of the trabecular bone network was more axially aligned in Chinese-American women because axial bone volume fraction was 51% and 32% higher at the distal radius and tibia, respectively, than in white women (p < .001). These striking differences in trabecular bone microstructure translated into 55% to 68% (distal radius, p < .001) and 29% to 43% (distal tibia, p < .01) greater trabecular bone strength, as assessed by Young's moduli, in the Chinese-American versus the white group. The observation that Chinese-American women have a major microstructural advantage over white women may help to explain why their risk of fracture is lower despite their lower BMD.

Vitamin D deficiency influences histomorphometric features of bone in primary hyperparathyroidism.

INTRODUCTION: Vitamin D deficiency is common in patients with primary hyperparathyroidism (PHPT). The presence of low levels of vitamin D may affect the skeletal consequences of PHPT. METHODS: In this cross-sectional study, transiliac crest bone biopsies were performed after double tetracycline labeling in patients with mild PHPT and analyzed according to serum levels of 25 hydroxyvitamin D (25OHD). RESULTS: We studied 30 patients with mild PHPT (age 53 ± 11 years; 67% women; calcium 11.1 ± 1.0 mg/dl; PTH 149 ± 129 pg/ml). Serum 25OHD levels were low in the majority of subjects (mean 21 ± 11 ng/ml) and inversely associated with PTH (r = -0.69; p < 0.01). 25OHD levels were directly associated with cortical width (Ct.Wi; r = 0.46, p < 0.03) and trabecular separation (Tb.Sp; r = 0.41; p < 0.04), but inversely associated with cancellous bone volume (BV/TV; r = -0.39, p < 0.04). Subjects with 25OHD levels < 20 ng/ml (n = 14) and ≥ 20 ng/ml (n = 16) were compared. Groups did not differ by age, sex, menopausal status, serum calcium, creatinine, or 1,25(OH)2D. PTH was 1.8-fold higher in subjects with 25OHD < 20 (265 ± 166 pg/ml vs. 95 ± 50 pg/ml; p < 0.01). On histomorphometric analysis, those with low 25OHD had lower Ct.Wi (541 ± 167 µm vs. 712 ± 200 µm; p < 0.03). Conversely, measures of trabecular microarchitecture were better in those with lower 25OHD, with higher BV/TV (26.1 ± 6.1% vs. 20.4 ± 6.4%; p < 0.03), greater trabecular number (Tb.N: 2.0 ± 0.4 mm⁻¹ vs. 1.8 ± 0.4 mm⁻¹; p < 0.04) and lower Tb.Sp (371 ± 90 µm vs. 472 ± 137 µm; p < 0.04). There were no differences between the groups in bone remodeling indices. CONCLUSIONS: Low levels of 25OHD in patients with PHPT are associated with higher concentrations of PTH, greater catabolic effects in cortical bone and greater anabolic effects in trabecular bone.

Application of high-resolution skeletal imaging to measurements of volumetric BMD and skeletal microarchitecture in Chinese-American and white women: explanation of a paradox.

Asian women have lower rates of hip and forearm fractures despite lower areal BMD (aBMD) by DXA compared with white women and other racial groups. We hypothesized that the lower fracture rates may be explained by more favorable measurements of volumetric BMD (vBMD) and microarchitectural properties, despite lower areal BMD. To address this hypothesis, we used high-resolution pQCT (HRpQCT), a new method that can provide this information noninvasively. We studied 63 premenopausal Chinese-American (n = 31) and white (n = 32) women with DXA and HRpQCT. aBMD by DXA did not differ between groups for the lumbar spine (1.017 +/- 0.108 versus 1.028 +/- 0.152 g/cm(2); p = 0.7), total hip (0.910 +/- 0.093 versus 0.932 +/- 0.134 g/cm(2); p = 0.5), femoral neck (0.788 +/- 0.083 versus 0.809 +/- 0.129 g/cm(2); p = 0.4), or one-third radius (0.691 +/- 0.052 versus 0.708 +/- 0.047 g/cm(2); p = 0.2). HRpQCT at the radius indicated greater trabecular (168 +/- 41 versus 137 +/- 33 mg HA/cm(3); p = <0.01) and cortical (963 +/- 46 versus 915 +/- 42 mg HA/cm(3); p < 0.0001) density; trabecular bone to tissue volume (0.140 +/- 0.034 versus 0.114 +/- 0.028; p = <0.01); trabecular (0.075 +/- 0.013 versus 0.062 +/- 0.009 mm; p < 0.0001) and cortical thickness (0.98 +/- 0.16 versus 0.80 +/- 0.14 mm; p < 0.0001); and lower total bone area (197 +/- 34 versus 232 +/- 33 mm(2); p = <0.001) in the Chinese versus white women and no difference in trabecular number, spacing, or inhomogeneity before adjustment for covariates. Similar results were observed at the weight-bearing tibia. At the radius, adjustment for covariates did not change the direction or significance of differences except for bone, which became similar between the groups. However, at the tibia, adjustment for covariates attenuated differences in cortical BMD and bone area and accentuated differences in trabecular microarchitecture such that Chinese women additionally had higher trabecular number and lower trabecular spacing, as well as inhomogeneity after adjustment. Using the high-resolution technology, the results provide a mechanistic explanation for why Chinese women have fewer hip and forearm fractures than white women.

The natural history of primary hyperparathyroidism with or without parathyroid surgery after 15 years.

CONTEXT: Primary hyperparathyroidism (PHPT) often presents without classical symptoms such as overt skeletal disease or nephrolithiasis. We previously reported that calciotropic indices and bone mineral density (BMD) are stable in untreated patients for up to a decade, whereas after parathyroidectomy, normalization of biochemistries and increases in BMD ensue. OBJECTIVE: The objective of the study was to provide additional insights in patients with and without surgery for up to 15 yr. DESIGN: The study had an observational design. SETTING: The setting was a referral center. PATIENTS: Patients included 116 patients (25 men, 91 women); 99 (85%) were asymptomatic. INTERVENTION: Fifty-nine patients (51%) underwent parathyroidectomy and 57 patients were followed up without surgery. MAIN OUTCOME MEASURE: BMD was measured. RESULTS: Lumbar spine BMD remained stable for 15 yr. However, BMD started to fall at cortical sites even before 10 yr, ultimately decreasing by 10 +/- 3% (mean +/- sem; P < 0.05) at the femoral neck, and 35 +/- 5%; P < 0.05 at the distal radius, in the few patients observed for 15 yr. Thirty-seven percent of asymptomatic patients showed disease progression (one or more new guidelines for surgery) at any time point over the 15 yr. Meeting surgical criteria at baseline did not predict who would have progressive disease. BMD increases in patients who underwent surgery were sustained for the entire 15 yr. CONCLUSIONS: Parathyroidectomy led to normalization of biochemical indices and sustained increases in BMD. Without surgery, PHPT progressed in one third of individuals over 15 yr; meeting surgical criteria at the outset did not predict this progression. Cortical bone density decreased in the majority of subjects with additional observation time points and long-term follow-up. These results raise questions regarding how long patients with PHPT should be followed up without intervention.

The role of nicotinic inhibition in ketamine-induced behavior.

UNLABELLED: Several anesthetic drugs are nicotinic antagonists at or below levels used for anesthesia, including ketamine and volatile anesthetics. In contrast, propofol does not inhibit nicotinic receptors. To determine the potential behavioral ramifications of nicotinic inhibition by ketamine, we determined the doses of ketamine required to induce immobility, impair the righting reflex, and cause analgesia in the absence and presence of several nicotinic ligands. Propofol was used as a control in similar experiments. When used as a sole anesthetic drug, 383 +/- 22 mg/kg ketamine intraperitoneally (IP) was required for immobility and 180 +/- 17 mg/kg IP impaired righting reflex. Propofol, 371 +/- 34 mg/kg IP, induced immobility whereas 199 mg/kg IP inhibited the righting reflex. Nicotinic antagonists had no effect on the dose of propofol or ketamine required for either end-point. When nociceptive responses were tested at subhypnotic doses, no pronociceptive or antinociceptive phase was identified for propofol, whereas analgesia was induced at ketamine doses larger than 60 mg/kg IP. The broad-spectrum nicotinic antagonist mecamylamine enhanced the analgesic action of ketamine. These findings are different than those seen with volatile anesthetics, where nicotinic inhibition is thought to be responsible for a pronociceptive action. Such a phase is possibly obscured by analgesia induced as a result of N-methyl-d-aspartic acid antagonism by ketamine. IMPLICATIONS: Ketamine and volatile anesthetics, but not propofol, inhibit neuronal nicotinic acetylcholine receptors in clinically relevant concentration ranges. Nicotinic inhibition by ketamine is not related to its immobilizing or sedating effects but may play a role in ketamine's analgesic action.