Previous fracture and subsequent fracture risk: a meta-analysis to update FRAX.

A large international meta-analysis using primary data from 64 cohorts has quantified the increased risk of fracture associated with a previous history of fracture for future use in FRAX. INTRODUCTION: The aim of this study was to quantify the fracture risk associated with a prior fracture on an international basis and to explore the relationship of this risk with age, sex, time since baseline and bone mineral density (BMD). METHODS: We studied 665,971 men and 1,438,535 women from 64 cohorts in 32 countries followed for a total of 19.5 million person-years. The effect of a prior history of fracture on the risk of any clinical fracture, any osteoporotic fracture, major osteoporotic fracture, and hip fracture alone was examined using an extended Poisson model in each cohort. Covariates examined were age, sex, BMD, and duration of follow-up. The results of the different studies were merged by using the weighted ß-coefficients. RESULTS: A previous fracture history, compared with individuals without a prior fracture, was associated with a significantly increased risk of any clinical fracture (hazard ratio, HR = 1.88; 95% CI = 1.72-2.07). The risk ratio was similar for the outcome of osteoporotic fracture (HR = 1.87; 95% CI = 1.69-2.07), major osteoporotic fracture (HR = 1.83; 95% CI = 1.63-2.06), or for hip fracture (HR = 1.82; 95% CI = 1.62-2.06). There was no significant difference in risk ratio between men and women. Subsequent fracture risk was marginally downward adjusted when account was taken of BMD. Low BMD explained a minority of the risk for any clinical fracture (14%), osteoporotic fracture (17%), and for hip fracture (33%). The risk ratio for all fracture outcomes related to prior fracture decreased significantly with adjustment for age and time since baseline examination. CONCLUSION: A previous history of fracture confers an increased risk of fracture of substantial importance beyond that explained by BMD. The effect is similar in men and women. Its quantitation on an international basis permits the more accurate use of this risk factor in case finding strategies.

Update of the fracture risk prediction tool FRAX: a systematic review of potential cohorts and analysis plan.

We describe the collection of cohorts together with the analysis plan for an update of the fracture risk prediction tool FRAX with respect to current and novel risk factors. The resource comprises 2,138,428 participants with a follow-up of approximately 20 million person-years and 116,117 documented incident major osteoporotic fractures. INTRODUCTION: The availability of the fracture risk assessment tool FRAX® has substantially enhanced the targeting of treatment to those at high risk of fracture with FRAX now incorporated into more than 100 clinical osteoporosis guidelines worldwide. The aim of this study is to determine whether the current algorithms can be further optimised with respect to current and novel risk factors. METHODS: A computerised literature search was performed in PubMed from inception until May 17, 2019, to identify eligible cohorts for updating the FRAX coefficients. Additionally, we searched the abstracts of conference proceedings of the American Society for Bone and Mineral Research, European Calcified Tissue Society and World Congress of Osteoporosis. Prospective cohort studies with data on baseline clinical risk factors and incident fractures were eligible. RESULTS: Of the 836 records retrieved, 53 were selected for full-text assessment after screening on title and abstract. Twelve cohorts were deemed eligible and of these, 4 novel cohorts were identified. These cohorts, together with 60 previously identified cohorts, will provide the resource for constructing an updated version of FRAX comprising 2,138,428 participants with a follow-up of approximately 20 million person-years and 116,117 documented incident major osteoporotic fractures. For each known and candidate risk factor, multivariate hazard functions for hip fracture, major osteoporotic fracture and death will be tested using extended Poisson regression. Sex- and/or ethnicity-specific differences in the weights of the risk factors will be investigated. After meta-analyses of the cohort-specific beta coefficients for each risk factor, models comprising 10-year probability of hip and major osteoporotic fracture, with or without femoral neck bone mineral density, will be computed. CONCLUSIONS: These assembled cohorts and described models will provide the framework for an updated FRAX tool enabling enhanced assessment of fracture risk (PROSPERO (CRD42021227266)).

Differences in homeostatic model assessment (HOMA) values and insulin levels after vitamin D supplementation in healthy men: a double-blind randomized controlled trial.

Vitamin D is thought to play a role in glucose metabolism. The aim of the present study was to determine the effect of vitamin D supplementation on markers of insulin sensitivity and inflammation in men without diabetes with vitamin D deficiency/insufficiency. In this 1-year double-blind randomized controlled trial, 130 men aged 20-65 years (mean age 47.52 ± 11.84 years) with serum 25-hydroxyvitamin D levels <50 nmol/l (mean 38.89 ± 8.64 nmol/l) were randomized to treatment (100 000 IU vitamin D bimonthly) or placebo. Anthropometric measurements, demographic questionnaires, and blood indices (fasting glucose, insulin, high-sensitivity C-reactive protein, lipids) were collected and repeated after 6 and 12 months. The compliance rate was 98.5%. Multivariate models, adjusted for baseline levels, age, body mass index, sun exposure, physical activity and LDL, showed significant differences in insulin and homeostatic model assessment of insulin resistance (HOMA-IR) values between groups. Levels of insulin and HOMA-IR values remained steady during the study period in the treatment group but increased by 16% in the control group (p = 0.038 and p = 0.048, respectively). Vitamin D supplementation administered for 12 months in healthy men maintained insulin levels and HOMA-IR values relative to the increase in the control group. Further studies are needed to establish the long-term effect of vitamin D supplementation on the risk of diabetes.

Association of gastrointestinal events and osteoporosis treatment initiation in newly diagnosed osteoporotic Israeli women.

BACKGROUND: The objective was to examine the association of gastrointestinal (GI) events and osteoporosis treatment initiation patterns among postmenopausal women following an osteoporosis diagnosis from an Israeli health plan. METHODS: This retrospective analysis of claims records included women aged ≥ 55 years with ≥ 1 osteoporosis diagnosis (date of first diagnosis was index date). Osteoporosis treatment initiation was defined as use of osteoporosis therapy (oral bisphosphonates or other) during 12 months postindex. GI events (diagnosis of GI conditions) were reported for 12 months preindex and postindex (from index to treatment initiation or 1 year postindex, whichever occurred first). The association of postindex GI events (yes/no) with the initiation of osteoporosis treatment (yes/no) and with type of therapy initiated (oral bisphosphonate vs. other) were examined with logistic regression and Cox proportional hazard regression (as sensitivity analysis). RESULTS: Among 30,788 eligible patients, 17.5% had preindex GI events and 13.0% had postindex GI events. About 70.6% of patients received no osteoporosis therapy within 1 year of diagnosis, 24.9% received oral bisphosphonates and 4.5% received other medications. Postindex GI events were associated with lower odds of osteoporosis medication initiation (85-86% reduced likelihood; p < 0.01). Upon treatment initiation, postindex GI was not significantly associated with the type of osteoporosis therapy initiated, controlling for baseline GI events and patient characteristics. CONCLUSIONS: Among newly diagnosed osteoporotic women from a large Israeli health plan, 70.6% did not receive osteoporosis treatment within 1 year of diagnosis. The presence of GI events was associated with reduced likelihood of osteoporosis treatment initiation.

Identifying the threshold for vitamin D insufficiency in relation to cardiometabolic markers.

BACKGROUND AND AIMS: To determine the association between vitamin D status and cardiometabolic indicators, and to determine the vitamin threshold that affects these parameters. METHODS AND RESULTS: High-tech employees were recruited from a periodic occupational health examination clinic and via the study's website. Diastolic and systolic blood pressure (DBP, SBP), body mass index (BMI), and waist circumference were measured. Serum concentrations of 25(OH)D, fasting plasma insulin (FPI), fasting plasma glucose (FPG), triglycerides (TG), and high sensitive C-Reactive Protein (hs-CRP) were measured in fasting blood samples. Of the 400 men who agreed to participate, 358 (90%) completed the study. Mean age was 48.8 ± 10.2 y, BMI 27.0 ± 3.8 k/m(2), serum 25(OH)D 22.1 ± 7.9 ng/l. Deficiency (defined as serum 25(OH)D < 12 ng/ml) was observed among 10.6%, 29.9% were insufficient (12 < 25(OH)D < 20 ng/ml), and 59.5% had sufficient levels (25(OH)D > 20 ng/ml). BMI, waist circumference, FPI, HOMA-IR, TG, hs-CRP levels, DBP, and SBP were negatively associated with serum 25(OH)D. A curved linear association was found with insulin and HOMA-IR with a significant spline knot at 11 ng/ml. For hs-CRP a spline knot at 14 ng/ml was observed. TG, SBP, and DBP exhibited linear associations with 25(OH)D. CONCLUSIONS: Vitamin D status is related to cardiometabolic indicators in healthy men. We suggest a 25(OH)D threshold of 11-14 ng/ml for these outcomes. Future studies are required to address temporal relationships and the impact of vitamin D supplementation.

Total versus hemithyroidectomy for microscopic papillary thyroid cancer.

BACKGROUND: No increased mortality has been reported in patients with thyroid papillary microcarcinoma (PMC); however, neck recurrences and distant metastases have been described. In this study, we compare patients' outcomes after total thyroidectomy vs hemithyroidectomy for treatment of thyroid PMC. METHODS: Two hundred and ninety-three patients from two major medical centers in Israel were included. The mean follow-up period was 7.2±6.8 yr. RESULTS: Total thyroidectomy was performed in 214 patients and hemithyroidectomy in 79 patients. Mean tumor size was 6.3±3 mm. Lymph-node (LN) metastases and extraglandular extension were more frequent in the total thyroidectomy group than in the hemithyroidectomy group, 24.8% vs 1.3% (p<0.001) and 11.7% vs 3.8% (p=0.042), respectively. The cumulative incidence of recurrence at the end of follow-up was 13.2% in the total thyroidectomy group and 14.3% in the hemithyroidectomy group (p=ns). The incidence of recurrence was higher in patients with LN involvement in both groups. Considering low risk patients only (monofocal tumors, no LN involvement, no extraglandular extension; no.=63 in the total thyroidectomy group vs no.=60 in the hemithyroidectomy group) neck recurrence was found in 10% of patients in the hemithyroidectomy group but none in the total thyroidectomy group. In the hemithyroidectomy group, all locoregional recurrences were diagnosed using ultrasonography, compared to 47.6% in the total thyroidectomy group. CONCLUSION: For patients with monofocal disease within the thyroid gland and no LN involvement, hemithyroidectomy can be considered an option, bearing in mind a higher risk for recurrence. For all other patients with PMC, we propose total thyroidectomy as initial treatment.

Severe postpartum osteoporosis with increased PTHrP during lactation in a patient after total thyroidectomy and parathyroidectomy.

We present a 27-year-old woman with hypoparathyroidism following total thyroidectomy for papillary carcinoma, who presented postpartum during lactation with several vertebral osteoporotic fractures, increase in bone turnover markers, and measurable parathyroid hormone-related protein (PTHrP) levels. Cessations of lactation led to gradual decrease in bone turnover markers and PTHrP and improvement in bone mineral density. Pregnancy- and postpartum-associated osteoporosis is an uncommon condition characterized by the occurrence of fractures during late pregnancy or the puerperium. The patient presented postpartum with severe back pain and multiple vertebral fractures. Metabolic evaluation performed at presentation revealed hypercalcemia, hypercalciuria, increased alkaline phosphatase, vitamin D insufficiency, normal serum protein immunoelectrophoresis, and a detectable level of PTHrP. Serum levels of bone turnover markers were markedly increased. Bone mineral density at the lumbar spine was severely reduced. After cessation of lactation, the PTHrP level became undetectable. Bone turnover markers gradually decreased to normal and bone mineral density improved. Several factors contributed to the reduced bone mass in this patient, including amenorrhea treated with oral contraceptives, suppressive levothyroxine treatment, and lactation of twins with increased PTHrP. Patients with severely reduced bone mass need surveillance during pregnancy and lactation and should possibly consider avoiding breastfeeding. Patients with hypoparathyroidism should temporarily reduce their alphacalcidiol dose while lactating.

Normal parathyroid hormone responsiveness of bone-derived cells from a patient with pseudohypoparathyroidism.

Pseudohypoparathyroidism (PHP) is characterized by a lack of response to parathyroid hormone (PTH); however, normal skeletal responsiveness to PTH in some patients with PHP type Ia was previously suggested on the basis of clinical observations. To test this hypothesis, we measured cyclic adenosine monophosphate (cAMP) production in response to various agonists in bone-derived osteoblast-like (OBL) cells from trabecular explants obtained from an iliac crest biopsy of a 25-year-old woman with PHP. The patient was proved to have PHP type Ia on the basis of Albright's hereditary osteodystrophy and decreased activity of stimulatory guanine nucleotide-binding protein (Gs) in erythrocytes. Responsiveness of the patient's OBL cells was compared with OBL cells from eight subjects aged 18-39 years who had no evidence of metabolic bone disease. OBL cells from the patient responded to the following agonists (expressed in multiples of elevation of cAMP, stimulated/basal, mean +/- SE, n = 3): PTH, 3.8 +/- 0.3; forskolin, 8.2 +/- 0.2; and cholera toxin, 56.8 +/- 10.0. These responses were not significantly different from those of control OBL cells: PTH, 4.5 +/- 1.1 (range 2.4-7.5); forskolin, 7.7 +/- 1.4; and cholera toxin, 57.9 +/- 16.2. The normal cholera toxin response indicated the presence of functional Gs. Bone cells from patients with PHP type Ia may exhibit a normal PTH receptor-coupled adenylyl cyclase system in vitro despite clinical evidence of impaired hormone-responsive adenylyl cyclase in other tissues, including the kidney. Skeletal responsiveness to PTH may explain the long periods of spontaneous normocalcemia observed in this patient.

Effect of antiinsulin-like growth factor 1 on epidermal proliferation of human skin transplanted onto nude mice treated with growth hormone.

Recently it has been demonstrated that long-term administration of GH leads to increase of skin thickness. The aim of the present study was to determine whether this effect of GH is mediated by insulin growth factor 1 (IGF-1), which enhances epidermal proliferation. In order to address this question, human split-thickness grafts obtained from aged skin were grafted onto nude mice. One group of mice was treated systemically with GH, whereas a second group was treated with intradermal graft injections of anti-IGF-1 in addition to GH. A third group received distilled water and served as a control group. Histological and autoradiographic analyses were performed before and after engraftment. The GH-treated mice showed a significant increase in epidermal proliferation measured by epidermal thickness (analysis of variance with repeated measurements, P < 0.01) and labeled index (analysis of variance, P < 0.01) as compared to the control group. The intradermal injections of anti-IGF-1 reduced significantly the proliferative stimulatory effect of GH (P < 0.01). The present study emphasizes the role of IGF-1 in the increased skin thickness observed after GH administration and provides a useful model for determining the effect of various compounds, including GH, on human skin.

Interleukin-6 modulates trabecular and endochondral bone turnover in the nude mouse by stimulating osteoclast differentiation.

A great deal of evidence has been accumulating that implicates the immune system in normal and pathological bone turnover. The objective of the present study was to examine the possible involvement of cytokines produced by T lymphocytes in bone metabolism. We have chosen the immunologically compromised athymic mouse, which demonstrate sclerotic features in its trabecular bone, as the animal model for assessment of possible modulation effects of interleukin-1alpha (IL-1alpha) and interleukin-6 (IL-6) on bone and cartilage metabolism. The cytokines were applied by daily subcutaneous injections for 3 consecutive days. Histomorphometry, measuring epiphyseal trabecular bone volume (ETBV), metaphyseal trabecular bone volume (MTBV), and the width of the growth plate, and tartrate-resistant acid phosphatase (TRAP) histochemistry were used to assess parameters of bone turnover in the proximal tibia. IL-6, but not IL-1alpha, reduced ETBV and MTBV. Both IL-6 and IL-1alpha reduced the width of the growth plate. IL-6, but not IL-1alpha, increased the number of chondroclasts and osteoclasts in the primary spongiosa of the proximal tibia, as well as the number of nuclei. The resultant bone resembled that of the wild-type mouse. The results point to IL-6 as a possible regulator of bone turnover in vivo. It is suggested that the athymic mouse has a deficiency somewhere in the cascade of events leading to the production of IL-6 or, alternatively, that IL-6 replaces other factors that are supplied by T lymphocytes directly or indirectly. As T lymphocytes interact with B lymphocytes it is suggested that the athymic mouse might be appropriate for studying the in vivo effects of the immune system on normal bone metabolism.

Goiter and hypothyroidism during re-treatment with amiodarone in a patient who previously experienced amiodarone-induced thyrotoxicosis.

A 55-year-old woman who had been receiving treatment with amiodarone for recurrent supraventricular tachyarrhythmias became thyrotoxic after 30 months of treatment. The thyroid gland was not enlarged or tender. Amiodarone was discontinued, and thyrotoxicosis gradually abated. A thyroid scan performed at that time revealed a gland of normal size and texture. Six months later, amiodarone treatment was reinstated due to life-threatening tachyarrhythmia; however, the patient remained euthyroid. Three years later, multinodular goiter began to develop, and 5 years after that, the patient became hypothyroid. Tests for thyroid autoantibodies, as well as inhibitory and stimulatory antibodies, were negative, and fine needle aspiration biopsy revealed an adenomatous goiter. Treatment with amiodarone was continued; however, therapy with L-thyroxin was initiated, followed by a complete regression of the goiter. The patient has since required a maintenance dose of L-thyroxin. The possible mechanisms by which iodine-containing drugs induce thyroid disfunction are reviewed, suggesting this case was caused by an alteration in the sensitivity of the intrinsic autoregulation of the thyroid gland to iodine.

Lithium treatment in amiodarone-induced thyrotoxicosis.

PURPOSE: Amiodarone hydrochloride is an iodine-rich drug effective in the control of various tachyarrhythmias. It is known to cause refractory to thyrotoxicosis, which usually does not respond to regular antithyroid drugs. Lithium bicarbonate is a medication used to treat psychiatric disorders; it also influences thyroid production and release of hormones. We tried it in combination with propylthiouracil (PTU) for the treatment of amiodarone-induced thyrotoxicosis. PATIENTS AND METHODS: Twenty-one patients were studied. The first group (n = 5) was treated by amiodarone withdrawal only. The second group (n = 7) received PTU (300 to 600 mg), and the third (n = 9) PTU (300 mg) and lithium (900 to 1350 mg) daily. Patient selection was not randomized. The PTU + lithium group had more severe symptoms and signs of thyrotoxicosis, as well as thyroxine levels at least 50% above the upper limit of normal. They also had been on a longer course of amiodarone treatment (34.3 +/- 11.9 months) than the PTU-only (11.4 +/- 7.5) and the no-treatment (7.8 +/- 4.2) groups. RESULTS: While there was no difference between the first two groups in time until recovery (10.6 +/- 4.0 versus 11.6 +/- 0.5 weeks, respectively), the group receiving lithium normalized their thyroid function tests in only 4.3 +/- 0.5 weeks (P < 0.01 versus both other groups). T3 levels normalized even earlier-by 3 weeks of lithium treatment. No adverse effects of lithium were encountered, and the medication was stopped 4 to 6 weeks after achieving a normal clinical and biochemical state. CONCLUSIONS: We conclude that lithium is a useful and safe medication for treatment of iodine-induced thyrotoxicosis caused by amiodarone. We would reserve this treatment for severe cases only. Further studies are needed to find out whether in patients with this troublesome complication lithium therapy could permit continuation of amiodarone treatment.

In vivo SPECT quantitation of bone metabolism in hyperparathyroidism and thyrotoxicosis.

Bone metabolism was assessed in vivo and noninvasively using quantitative SPECT. The effect of endocrine abnormalities on bone metabolism was studied in 27 patients with primary hyperparathyroidism (HPT) and 12 patients with thyrotoxicosis (TTX). Quantitative bone scintigraphy (QBS) values of 99mTc-MDP uptake were compared to normal values matched for sex and age. Bones with significantly increased QBS values indicating increased bone metabolism were identified in the two patient groups. Fifty-one percent of the bones in patients with HPT and 78% in patients with TTX showed significantly increased QBS values. Increase in bone metabolism was highest in the femoral shaft. Seven patients with HPT and five with TTX were successfully treated. Six patients with HPT and four patients with TTX showed significant decrease of bone metabolism with normal QBS values after three months. The results indicate that QBS can be used to evaluate bone metabolism and its response to treatment in individual bones in patients with endocrine abnormalities.

SPECT quantitation of iodine-131 concentration in phantoms and human tumors.

The validity of SPECT measurement of iodine-131 (131I) concentration was tested in vitro in phantoms and in vivo by measuring bladder urine concentrations. Phantom studies comparing known and SPECT measured concentrations showed a good correlation for 131I (r = 0.98, s.e.e. = 20.94 counts/voxel) for phantoms of 25 to 127 cc and concentrations of 0.13 to 9.5 microCi/cc. The in vivo, in vitro correlation of 131I concentrations in the urine was also good (r = 0.98, s.e.e. = 0.677 microCi/cc). Quantitative SPECT was used to calculate the effective half-life and dosimetry of radioiodine in 12 sites of thyroid carcinoma in seven patients. SPECT was also used to determine the dosimetry of [131I]MIBG (metaiodobenzylguanidine) in two patients with carcinoid, two with neuroblastoma, and one with pheochromocytoma. The radiation dose for thyroid carcinoma metastases varied between 6.3 and 276.9 rad/mCi. The dose from MIBG varied between 13.4 and 57.8 rad/mCi. These results indicate the validity of quantitative SPECT for in vivo measurement of 131I and the need to measure the concentration of 131I in individual human tumor sites.

The distal axis of growth hormone (GH) in nutritional disorders: GH-binding protein, insulin-like growth factor-I (IGF-I), and IGF-I receptors in obesity and anorexia nervosa.

The endocrine abnormalities along the growth hormone (GH) axis in anorexia nervosa (AN) and in obesity include hypothalamic, pituitary, and peripheral elements. The present study was undertaken to evaluate the effects of these nutritional extremes on GH-binding protein (BP) levels and on Insulin-like growth factor-I (IGF-I) receptors on red blood cells (RBC). Nine patients with AN and 20 obese subjects were compared with normal control children, adolescents, and adults. GH-BP was measured by a binding assay with dextran-coated charcoal separation. IGF-I binding was measured on enriched RBC. Serum GH-BP levels were markedly reduced in the AN patients, and highly increased in the obese. Scatchard analyses showed linear plots with unaltered binding affinities (Ka). The binding capacity (Bmax) was significantly lower than normal control in the AN patients and higher in the obese. GH-BP levels correlated positively with the body mass index (BMI). RBC [125I]IGF-I binding was significantly elevated in the AN patients and low in the obese. Scatchard analyses showed curvilinear plots. The high-affinity constants (Ka1) were slightly, but significantly, higher in the AN patients and in the obese compared with control. The binding capacity of the first binder (Bmax1) was lower in obesity than in AN or control. The low-affinity constants (Ka2) were similar in the three groups, and its binding capacity (Bmax2) was similar in the AN patients and the controls, but significantly lower in the obese. [125I]IGF-I binding correlated negatively and significantly with the BMI and with the GH-BP.(ABSTRACT TRUNCATED AT 250 WORDS)

Low titer, competitive insulin autoantibodies are spontaneously produced in autoimmune diseases of the thyroid.

The occurrence of multiple endocrine autoimmunity with organ-specific autoantibodies is well known. In this study we evaluated the presence of competitive insulin autoantibodies (IAA) in immune and non-immune diseases of the thyroid, utilizing a sensitive and specific radiobinding assay. We studied 37 patients with Graves' disease, 44 patients with Hashimoto's thyroiditis, 11 patients with non-immune thyroid diseases and 30 normal controls. In 5/37 (13.5%), 7/44 (15.9%) patients with Graves' and Hashimoto's diseases, respectively, but in none of those with non-immune thyroid disease or of the controls, IAA levels exceeded our upper limit of normal range (50 nunits/ml) (P < 0.01). Positive IAA levels ranged between 50 and 123 nunits/ml with fluctuation of these levels over time. Islet cell antibodies were not detected in any of the patients and the controls in the study. No association was found between propylthiouracile treatment and level of IAA. In none of 10 IAA-positive patients was the early phase insulin secretion of the intravenous glucose tolerance test below 46 mu units/ml, and in 2 subjects repeated tests after 3 years showed conserved insulin secretion. In conclusion, our findings show that 15% of patients with autoimmune thyroid diseases, produce specific IAA which do not seem to reflect aggressive beta cell destruction.

Oral complaints related to menopause.

OBJECTIVES: The purpose of the present study was to correlate oral and systemic symptoms of menopause and the oral health and salivary composition and flow rate in a group of women in menopause prior to hormone replacement therapy. METHODS: One-hundred fifty-four women attending a menopause clinic were divided into two groups. Group A, 58 women, without any systemic disease or treatments, and Group B,96 women with diseases and on various medications. They answered a questionnaire on their general health and oral and systemic complaints related to menopause. Fifty-four of the women agreed to have an oral examination and saliva analysis. Whole resting and submandibular (SM-SL) stimulated saliva were analyzed. RESULTS: The oral discomfort complaint was found in 45% in Group A and in 60% in Group B. 74% complained of climacteric symptoms in Group A and 63% in Group B. The odds ratio (OR) between oral discomfort and climacterics complaints of menopause was 8.03 in Group A and 4.08 in Group B. The salivary composition and flow rates did not differ significantly between the groups of menopausal women. However the salivary total protein and IgA concentrations were significantly higher in comparison to healthy young controls. CONCLUSIONS: The present study reports a high prevalence of oral discomfort in the women attending a menopause clinic. A highly significant odds ratio between systemic and oral complaints of menopause was found. The significantly altered salivary composition in these women might point to sympathetic activation due to psychological stress.

Effect of estrogen replacement therapy on speed of sound at multiple skeletal sites.

OBJECTIVES: To evaluate the effect of estrogen replacement therapy (ERT) on postmenopausal bone loss by multi-site ultrasound measurement. METHODS: A cross-sectional comparison of postmenopausal women, ERT users and non-users. The two study groups were enrolled for the reference database collection for the Sunlight Omnisense (Omnisense) and were matched by years since menopause. Speed of sound (SOS) was measured at the distal radius (RAD), mid-shaft tibia (TIB), fifth metatarsus (MTR) and proximal phalanx (PLX). RESULTS: 143 ERT users for 5.2+/-3.6 years were compared with 139 ERT non-users (age: 57.0+/-5.3 and 57.5+/-5.5, respectively). Both groups were 7.1+/-5.0 years since menopause. SOS, expressed in T-score units, was higher at the RAD in ERT users as compared to ERT non-users (-0.55+/-1.30 and -1.36+/-1.60, respectively, P<0.0001), and at the TIB (-0.73+/-1.34 and -1.28+/-1.45, respectively, P=0. 003). Same trend was observed at the MTR and PLX, but not statistically significant because of fewer observations. In early post menopause period, the ERT-non users RAD data shows an annual SOS decrease of 0.17 versus annual increase of 0.12 T-score units (P=0.037). Similar effect is observed at the TIB, though not statistically significant (non-users decrease of 0.20 vs. users increase of 0.08 T-score units/year, P=0.086). CONCLUSIONS: SOS measurements by Omnisense at multiple skeletal sites support the ERT protective effect on bone.