Utilization profile of emergency department by irregular migrants and hospitalization rates: lessons from a large urban medical center in Tel Aviv, Israel.

BACKGROUND: Irregular migrants (IMM) are excluded from the National health insurance in most developed countries and may use the emergency department (ED) as a source for medical care. This study aims to compare the use of ED by IM with that of Israeli citizens (IC) in a large urban hospital in Tel Aviv, including socio-demographic characteristics, hospitalization proportion and medical conditions on admission. METHODS: This cross-sectional study included all IM and IC patients older than 18 years who attended the ED between 2007 and 2011, and compared their socio-demographic characteristics, the administrative details of the visit and clinical variables upon admission. Hospitalization proportion was calculated by dividing the number of patients who were admitted to the hospital ward by the number of all patients who attended the ED. RESULTS: IM who attended the ED were younger compared to IC (mean 39 ± 17 versus 52 ± 22 years, respectively), mostly males (1.4 Male/Female ratio) and mainly originated from developing countries. IM were more commonly self-referred, more likely to attend the ED during evening hours and weekends, complained of occupational injuries and frequented the surgical rather the medical ward of the ED compared with IC. IM stayed at the ED for longer periods than IC, yet the proportion of their hospitalization was lower than that of IC (19.4% versus 23.5%, respectively). CONCLUSION: IM stayed in the ED for longer periods and were less likely to be admitted to the hospital wards, suggesting presentation of non-severe medical conditions or possible barriers in ensuring care continuity in the community following discharge. Minimizing the barriers of IM to primary care in the community can reduce unnecessary referrals to the ED. Additionally, hospitals managements should respond to the high-volume of IM by shifting staff to busy hours and improving the communication with IM.

HIV infection among men who have sex with men in Israel: a 35-year epidemiological and clinical overview, 1981-2015.

BACKGROUND: This study is the first to describe major epidemiological trends and clinical characteristics among Israeli men who have sex with men (MSM), who are at a higher risk for HIV infection. METHODS: This retrospective study includes all individuals reported to the Israeli Ministry of Health with HIV and self-identified as MSM between 1981 and 2015. The incidence rates of HIV infection and AIDS-defining diseases were analyzed and Kaplan-Meier survival estimates were calculated from time of HIV infection notification to AIDS diagnosis and death across three consecutive periods representing antiretroviral treatment availability. RESULTS: The trend of increase in HIV incidence is similar to Western Europe, although Israeli rates are lower. Of 2052 HIV/AIDS Israeli MSM diagnosed during the follow-up, 296 (14.6%) developed AIDS. MSM constitute 28.4% of all HIV/AIDS cases and 41.5% of cases among men. Average times from HIV-notification until AIDS diagnosis were 15.5 [14.0-16.9], 16.0 [15.5-16.4], and 6.7 [6.7-6.8] years, within 1981-1996, 1997-2007, and 2008-2015, respectively. The HIV-incidence rate among Israeli MSM slightly declined from 2012, after peaking in 2011 at 6.2 per 100,000. CONCLUSIONS: The recent reduction in HIV-incidence and in AIDS diagnoses among Israeli MSM is encouraging. Nevertheless, the disproportionate incidence of HIV among MSM requires sustained efforts to abate further infections.

Mother-to-child HIV transmissions in Israel, 1985-2011.

Mother-to-child transmission (MTCT) is the leading cause of paediatric HIV-infection in Israel. This study aimed to assess MTCT rates and analyse temporal changes in relation to highly active antiretroviral therapy (HAART) introduction in 1996. This historical prospective study included all HIV-infected women who delivered in Israel between 1988 and 2011. Demographic, clinical, laboratory and therapy characteristics were compared between HIV-infected newborns with all others, and between infants born before and after 1996. Of all 796 infants born in Israel to HIV-infected women, 25 (3·1%) were infected. MTCT rates decreased significantly after HAART introduction compared with infants who were born before 1996 (16·3% vs. 1·7%). Mothers who infected vertically were more likely to be younger, Ethiopian-born, delivered trans-vaginally, not treated with HAART during pregnancy/labour and delivered before 1996 compared with mothers who did not transmit the HIV to their neonates. Newborns who did not receive antiretroviral therapy postpartum were more commonly HIV-infected and their mortality rate was higher. In conclusion, HAART during pregnancy/labour decreased MTCT significantly. Most MTCT in Israel was recorded among Ethiopian migrants, yet, in decreasing rates. Continuous efforts should be employed to encourage early HIV testing and allow effective HAART to pregnant women who belong to a key risk-group.

Arab men who have sex with men in Israel: knowledge, attitudes and sexual practices.

OBJECTIVES: Arab men who have sex with men (AMSM) are becoming visible in society, and reports of HIV infection and sexually transmitted infections (STIs) are emerging. This study aimed to assess the knowledge of AMSM regarding HIV transmission, their attitudes towards condom use and their sexual practices compared with Jewish MSM (JMSM), and to evaluate AMSM-JMSM friendships and sexual encounters. METHODS: Participants in this cross-sectional study completed questionnaires in Arabic or Hebrew. The outcome variable was unprotected anal sex (UAI) in the previous 6 months with a partner(s) whose HIV status was discordant or unknown. AMSM and JMSM indicated if they had friends or sexual encounters from the other ethnic group. RESULTS: The questionnaires were completed by 342 (16.2%) AMSM and 1775 (83.8%) JMSM in 2012. AMSM were more likely to be religious, 'closeted' and married than JMSM; their knowledge regarding HIV transmission was inferior and attitudes towards condom use were less favourable. AMSM reported less alcohol and drug use than JMSM, were more likely to be attracted to and have sex with women, and reported a greater number of sexual partners and more UAI. Being AMSM was a predictive variable for UAI in the multivariate model. While 178 AMSM (52.0%) reported that most of their close friends were JMSM, 251 (73.4%) had only/mostly sexual encounters with JMSM. Among JMSM, 41 (2.3%) reported that their close friends were AMSM, and 308 (17.3%) had only/mostly sexual encounters with AMSM. CONCLUSIONS: The knowledge of AMSM regarding HIV transmission and their attitudes towards condom use were less favourable than those of JMSM, and they performed more UAI. AMSM may benefit from targeted interventions, including reconciling their same-sex attraction in positive terms. Same-sex attraction and gay identity may provide common ground to strengthen Arab-Jew communication in Israel.

Tuberculosis in native Israeli Arabs and Jews: trends and treatment outcomes, 1999-2011.

The incidence of tuberculosis (TB) in native ethnic minorities remains high in developed countries. Arabs, the major ethnic minority in Israel, comprise 21% of its population. This retrospective study compared TB incidence, demographic, clinical, laboratory, genotyping characteristics and treatment outcomes in all Israeli-born citizens diagnosed with TB between 1999 and 2011 by ethnicity, i.e. Israeli-born Arabs (IA) and Jews (IJ). A total of 831 Israeli-born TB patients were reported. Of those, there were 530 (64%) IJ and 301 (36%) IA, with an average annual TB rate of 1·1 and 1·6 cases/100 000 population, respectively, lower than the national average (7·0 cases/100 000 population). TB rates in IA and IJ declined and converged to 1 case/100 000 residents. IA TB patients were more likely to be older, have more pulmonary TB and have lower treatment success rates than IJ. Older age and HIV co-infection, but not ethnicity, were predictive of non-success in TB treatment. Ten mixed IA-IJ clades were detected by spoligotyping and three mixed IA-IJ clusters were identified by MIRU-VNTR typing. Only one IA-IJ couple recalled mutual contact. In conclusion, TB rate in IA was higher than in IJ, but declined and converged in both to 1 case/100 000. Treatment success was high in both groups, and was unrelated to ethnicity.

Increasing trend of HIV/AIDS among Arab and Jewish male persons in Israel, 1986-2010.

OBJECTIVES: The aim of the study was to compare the HIV/AIDS burdens in Jewish and Arab Israeli males, as HIV/AIDS affects different population groups disproportionally. METHODS: The National HIV/AIDS Registry (NHAR) was used as the source of HIV/AIDS infection records, while the Israeli Central Bureau of Statistics was used to determine group-specific disease rates. RESULTS: Between 1986 and 2010, 3499 HIV/AIDS-infected male Israelis were reported to the NHAR: 3369 (96.3%) Jews and 130 (3.7%) Arabs, with an average annual incidence of 5.5 and 0.8 per 100 000 of the population, respectively (P = 0.05). Of the Jews, 1018 (29.9%) were born in Ethiopia, while 2389 were Jews who were not Ethiopian-born (JNE). Most of the Arabs (n = 99; 74.8%) were Muslims, followed by Christians (21; 16.2%) and Druze (13; 10%). AIDS rather than HIV infection at the time of reporting was diagnosed in 568 (23.8%) of the JNE and 31 (23.8%) of the Arabs (p = 1). The most affected age group was those aged 25-34 years among the JNE and those aged 20-24 years among the Arabs, and the respective cumulative death rates were 24.9% (n = 594) and 32.5% (n = 40) (P = 0.1). The point prevalences in 2010 were 58.4 and 11.4 per 100 000 for JNE and Arabs, and in adults aged 15-59 years they were 71.5 and 26.3 per 100 000, respectively. In Muslims, Christians and Druze, the point prevalences were 4.2, 11.2 and 7.1 per 100 000, and in adults aged 15-59 years they were 22.6, 42.9 and 29.4, respectively. The most common risk group among JNE was men who have sex with men (MSM; n = 1223; 51.2%), followed by injecting drug users (n = 661; 27.7%), while among Arabs it was MSM (n = 63; 48.1%), followed by heterosexuals (n = 36; 27.3%). CONCLUSIONS: The HIV/AIDS burden in Israeli Arab males was significantly lower than that in Jews, and in both populations the most common risk group was MSM, with the proportion of MSM increasing with time.

Tuberculosis diagnostic delay and therapy outcomes of non-national migrants in Tel Aviv, 1998-2008.

Non-national migrants have limited access to medical therapy. This study compares diagnostic delay and treatment outcomes of non-insured non-national migrants (NINNM) with insured Israeli citizens (IC) in the Tel Aviv tuberculosis (TB) clinic between 1998 and 2008. Patient delay was the time from symptoms onset to doctor's visit, while system delay was measured from doctor visit to anti-TB therapy administration. We randomly sampled 222 NINNM and 265 IC. NINNM were younger than IC, had lower male to female ratio and fewer smoked. They had less drug/alcohol abuse, more cavitations on chest radiography, longer patient and shorter system delay. Mean patient and system delays of all patients were 25 ± 14 and 79 ± 42 days, respectively. In multivariate analysis, being NINNM, asymptomatic or smoking predicted longer patient delay, while being asymptomatic or having additional co-morbidity predicted longer system delay. Treatment success in sputum smear-positive pulmonary TB NINNM was 81% and 95.7% in IC (p=0.01). Treatment success was not associated with patient or system delay. In multivariate analysis, work security and treatment adherence predicted treatment success. NINNM had longer patient delay and worse therapy outcome, while IC had longer system delay. Both delays should be reduced. NINNM should be informed that TB therapy is free and unlinked with deportation.

Humidifier-associated paediatric Legionnaires' disease, Israel, February 2012.

We report a fatal case of community-acquired Legionnaires' disease in an infant aged under six months. Epidemiological and microbiological investigations suggested that a free-standing cold water humidifier using domestic tap water contaminated with Legionella pneumophila serogroup 1 served as a vehicle for infection. These findings were corroborated by sequence-based typing (SBT). Humidifier-associated Legionnaires' disease can be prevented by appropriate control measures. This case also illustrates the emerging role of SBT in the investigation of legionellosis.

Hepatitis A disease following the implementation of universal vaccination: who is at risk?

The incidence of acute hepatitis A in Israel has decreased 25 folds in less than a decade, following the introduction of a two-dose universal toddler's hepatitis A immunization in July 1999. This retrospective study describes demographic data and behavioural determinants of hepatitis A patients following the implementation of a vaccination programme. All records of hepatitis A patients reported to the Ministry of Health during the years 2003 through 2005 were reviewed, and an epidemiological investigation was conducted. During the study period, 420 hepatitis A patients were reported, representing an average annual incidence of two per 100,000 population. Case fatality rate was 0.5%. The majority of the patients were younger than 15 years of age, males and non-Jewish. The highest incidence was recorded in east Jerusalem, where vaccine coverage is relatively low. After exclusion of 165 east Jerusalem patients, 133 (52.2%) patients were available for an interview. Of those, 16 (6%) had possible occupational exposure, 37 (27.8%) travelled to endemic areas, 44 (17%) were contacts of hepatitis A cases, and 3 male patients had sex with men. No known risk determinant was identified in 33 (24.8%) patients. Four patients (3%) were previously immunized with one dose, and none had two doses. The introduction of universal toddler hepatitis A vaccination decreased morbidity. Most of the patients who were detected 4-6 years after the implementation of the vaccination programme could be classified into one of the known risk groups for hepatitis A infection or living in a partly vaccinated community.

Pre-immigration screening process and pulmonary tuberculosis among Ethiopian migrants in Israel.

More than 75,000 displaced Ethiopians have moved to Israel. Tuberculosis (TB) incidence in Ethiopia is 44 times higher than in Israel (344 versus 8 cases per 100,000 inhabitants, respectively). The aims of the present retrospective cohort study were to evaluate the pre-immigration screening process initiated in 2001 on pulmonary TB (PTB) morbidity and to assess its cost-effectiveness. Ethiopian immigrants who were screened before departure (study group) were compared with those who were screened after arrival (comparison group). Between 1998 and 2005, 24,051 Ethiopian immigrants arrived in Israel. PTB was diagnosed in 332 (1.4%) immigrants, an incidence density of 325 patients per 100,000 person-yrs. PTB cumulative incidence was lower in the study group than in the comparison group: 711 compared with 1,746 patients per 100,000 immigrants, respectively (rate ratio 0.4). PTB was detected significantly earlier in the study group than in the comparison group: 193 versus 487 days after entry, respectively. Disease incidence declined significantly during the first 2 yrs following immigration. A 5-yr predictive model indicated that 98 individuals would be free of PTB, saving US$91,055 on annual treatment cost, due to screening. The pre-immigration screening process reduced pulmonary tuberculosis incidence in subsequent years following immigration. Pulmonary tuberculosis was diagnosed earlier in the screened group than in the comparison group and the process was found to be both cost-beneficial and cost-effective.

Comparison of tuberculosis surveillance systems in low-incidence industrialised countries.

The comparative analysis of National Tuberculosis Control Programmes (NTPs) in industrialised, low-tuberculosis-incidence countries is limited. Analysis of applied methods, function and accumulated experience contributes to improving global tuberculosis control. A questionnaire addressing NTP surveillance infrastructure and characteristics was completed in 19 industrialised countries, with populations of >3 million and annual notified tuberculosis incidence rates of <16 cases per 100,000 population (2003 data). All European countries surveyed adopted World Health Organization Collaborating Centre for the Surveillance of Tuberculosis in Europe (EuroTB) definitions. Surveillance information, which usually includes names, was transferred electronically to the national level in 17 out of the 19 countries. Surveillance systems capture process and social determinants. Case notification to the central level occurred within a median period of 7 days, independent of mandatory notification requirements. The mean completeness of tuberculosis case-reporting was estimated to be 93.5% (range 65-100%). Integration between HIV and tuberculosis registries was performed in two countries, and, in seven others, both databases were cross-matched periodically. National Tuberculosis Control Programme function in industrialised low-incidence countries utilises well-established infrastructure and relies upon centralised operations. Approaches are consistent with current World Health Organization surveillance recommendations. The present study lays collaborative groundwork for additional multinational analyses for the enhancement of global tuberculosis surveillance, which may assist policy-makers in countries moving from medium to low rates of incidence.

Gay men who engage in substance use and sexual risk behaviour: a dual-risk group with unique characteristics.

'Recreational' substances used among men having sex with men, and their association with risky unprotected anal intercourse (RUAI) were examined--for the first time in Israel--in an internet-based questionnaire assessing knowledge, practices and motivation. Between March and May 2005, 2873 participants completed the entire questionnaire. Of the total, 669 (23%) reported RUAI during the last six months, and 1319 (46%) used substances during sex. Use of substance was significantly higher among those performing RUAI than those who did not (31.5% versus 26.4%, P=0.03). Involvement in both substance use and RUAI was reported by 366 participants (13%). HIV rates were higher in this dual-risk group (P<0.01), and individuals reported more partners in the last six months than those not part of this dual risk (11.6 versus 8.2, P=0.02). In multivariate analyses, Tel-Aviv residency, lower education, performing receptive RUAI, misperception of HIV transmission and limited negotiation skills were positively associated with this dual-risk behaviour.

Tuberculosis outbreak in a nursing home involving undocumented migrants and Israeli citizens.

ABSTRACK: OBJECTIVES: Israel has absorbed > 60,000 migrant from the horn of Africa (MHOA) since 2006. No cross-transmission of Mycobacterium tuberculosis from MOHA to Israeli citizens has yet been reported. This study describes the results of contact investigation and laboratory work-out of a unique mixed cluster which included both MOHA and Israeli citizens. METHODS: Description of the results of epidemiological investigation including laboratory confirmation. RESULTS: This unique Mycobacterium tuberculosis strain included 29 patients: 26 were MOHA and three citizens who immigrated to Israel from the former Soviet Union. This is the first mixed cluster described in Israel, which has not been represented in the SITVIT international database of genotyping markers. The transmission from non-citizens to citizens occurred in a nursing institution, when MOHA infected three other contacts- two of whom were retarded residents, one of them died. The index case was screened before employment, and was permitted to return to wok although his chest X-ray demonstrated radiological findings compatible with tuberculosis. Epidemiological links were found in other 12 MOHA members of the cluster. CONCLUSION: This report describes cross-transmission of Mycobacterium tuberculosis from non-citizens MOHA to Israeli citizens who were residents of a nursing home, which may be the first sign for an epidemiological shift. Although cross-ethnical transmission is still rare in Israel, medical settings should employ efficient infection control measures to protect both patients and staff from Mycobacterium tuberculosis.

Tuberculosis in migrants in low-incidence countries: epidemiology and intervention entry points.

As tuberculosis (TB) rates continue to decline in native populations in most low TB incidence countries, the proportion of TB patients born outside their country of residence ('foreign-born') increases. Some low-incidence countries have experienced a substantial increase in TB rates related to recent increases in the number of asylum seekers and other migrants from TB-endemic countries. However, average TB rates among the foreign-born in low-incidence countries declined moderately in 2009-2015. TB in foreign-born individuals is commonly the result of reactivation of latent infection with Mycobacterium tuberculosis acquired outside the host country. Transmission is generally low in low-incidence countries, and transmission from migrants to the native population is often modest. Variations in levels and trends in TB notifications among the foreign-born are likely explained by differences and fluctuations in the number and profile of migrants, as well as by variations in TB control, health and social policies in the host countries. To optimise TB care and prevention in migrants from endemic to low-incidence countries, we propose a framework for identifying possible TB care and prevention interventions before, during and after migration. Universal access to high-quality care along the entire migration pathway is critical. Screening for active TB and latent tuberculous infection should be tailored to the TB epidemiology, adapted to the needs of specific migrant groups and linked to treatment. Ultimately, the long-term TB elimination goal can be reached only if global health and socio-economic inequalities are dramatically reduced. Low-incidence countries, most of which are among the wealthiest nations, need to contribute through international assistance.

Seasonality of tuberculosis in Israel, 2001-2011.

BACKGROUND: Several studies have suggested that the incidence of tuberculosis (TB) varies with the seasons. OBJECTIVE: To determine the seasonality of TB in Israel and to explore possible associations with climatic variables. METHODS: Laboratory-confirmed TB cases reported between 2001 and 2011 in individuals resident in Israel for at least 1 year before diagnosis were included in the study. Climatic variables included average temperature and average ultraviolet radiation. The mean serum 25-hydroxyvitamin D level of the population was also recorded. RESULTS: Of all 2653 TB cases, incidence peaked during spring (n = 712) and reached its nadir during the fall (n = 577), with a case proportion amplitude (CPA) of 5.1% (P = 0.036). Individuals born in the Horn of Africa exhibited a CPA of 9.5% (P = 0.077). Mean population 25-hydroxyvitamin D level was significantly correlated with the seasonal pattern of the disease. Southern Israel had the highest global radiation and, counter-instinctively, the highest TB incidence. CONCLUSIONS: TB exhibited a seasonal tendency in Israel, with the spring peak/fall nadir pattern found elsewhere. Vitamin D is suspected to be an explanatory variable for this seasonal phenomenon. The finding that the highest incidence is in the area receiving the highest global radiation suggests population-related vulnerability to vitamin D deficiency.

Mortality after anti-tuberculosis treatment completion: results of long-term follow-up.

BACKGROUND: Mycobacterium tuberculosis affects the lung parenchyma even after successful treatment. OBJECTIVE: To assess long-term mortality in a cohort of individuals who had recovered from tuberculosis (TB), and to compare their mortality rate and causes of death with those of the general population. METHODS: This retrospective cohort study of all Israeli citizens who recovered from tuberculosis between 2000 and 2010 included all patient files and death certificates and/or hospitalisation records of deceased individuals. Death rates were computed using standard mortality rates (SMR). Cox proportional hazard regression was conducted to identify risk factors for death, and causes of death were compared with those in the general Israeli population. RESULTS: Over 11 years of follow-up, comprising 18,246 person-years, 389 (12.0%) Israeli citizens died after completion of anti-tuberculosis treatment, giving an SMR of 3.7. The SMR was strongly correlated with age, and was highest in males and individuals aged 25-44 years. Compared to the general population, among individuals who recovered from TB there were more deaths due to septicaemia and pneumonia, and fewer deaths due to cerebrovascular diseases, stroke and diabetes (P < 0.05). CONCLUSIONS: Individuals who recover from TB are at higher risk of long-term mortality than the general population, and their causes of death are different. Periodical follow-up might be beneficial for individuals to facilitate early diagnosis.

Age dependence and modulation by gonadectomy of the sex-specific response of rat diaphyseal bone to gonadal steroids.

We have previously reported that diaphyseal bone of prepubertal rats responds in a sex-specific manner to gonadal steroids, 24 h after steroid injection, by increases in creatine kinase (CK) specific activity and the rate of DNA synthesis. We have also shown that hormonal intervention abolished the sex-specific response of diaphyseal bone to sex steroids. In the present study, we examined the responsiveness of diaphyseal bone and cartilage to gonadal steroids in male and female Wistar-derived rats at ages between 5 days and 1 yr. In both diaphyseal bone and cartilage of untreated control rats, a peripubertal peak of CK specific activity was seen, which was more pronounced in females. Diaphyseal bone, unlike epiphyseal cartilage, responded specifically to a single injection of 17 beta-estradiol (E2; 5 micrograms/rat) in females and to 5 alpha-dihydrotestosterone (DHT; 50 micrograms/rat) in males. The highest response occurred peripubertally, but was skewed toward prepubertal ages in males and postpubertal ages in females. To study the effect of gonadectomy on this sex-specific response of diaphyseal bone, rats were gonadectomized at the age of 24 or 180 days and from 4 days to 4 weeks thereafter were challenged with either E2 or DHT. Diaphyseal bones of gonadectomized rats of either sex responded to both E2 and DHT, beginning 7 days after surgery. Thus, in gonadectomized rats, there was a loss of the sex specificity of response to steroid hormones, which could be restored by replenishment, by five daily injections, of the characteristic hormone of each sex. In the epiphyseal cartilage, the same replenishment schedule resulted in acquisition of a sex-specific response in both sexes, not seen previously. These data in conjunction with the previously reported hormonal modulation of sex-specific responses, are consistent with a developmental acquisition of diaphyseal sex steroid specificity that requires for its maintenance the presence of appropriate amounts of the characteristic gonadal steroid in each sex.

Regulation of proliferation of rat cartilage and bone by sex steroid hormones.

We have demonstrated previously that 17 beta-estradiol (E2) stimulates proliferation of skeletal tissues, both in vivo and in vitro, as measured by increased DNA synthesis and creatine kinase (CK) specific activity. The effect of E2 on bone is sex specific. E2 is active only in females and androgens only in males. By contrast, in cartilage of both sexes, dihydrotestosterone (DHT) as well as E2 stimulates CK specific activity and DNA synthesis. In bone, we find that sex steroids stimulate skeletal cell proliferation in gonadectomized as well as in immature rats. Ovariectomized (OVX) rats, between 1 and 4 weeks after surgery, show stimulation of CK by E2. The basal activity and response of CK changes with the varying endogenous levels of E2 in cycling rats, in which the highest basal activity is at proestrus and estrus and the highest response is in diestrus. In rats of all ages tested, both the basal and stimulated specific activity of CK is higher in diaphysis and epiphysis than in the uterus, or in the adipose tissue adjacent to the uterus, which has a response similar to that of the uterus itself. The effect of E2 in vivo, and in chrondroblasts and osteoblasts in vitro, is inhibited by high levels of the antiestrogen tamoxifen which, by itself, in similar high concentrations, shows stimulatory effects. In addition to the sex steroids, skeletal cells are also stimulated by secosteroid and peptide calciotrophic hormones. The interactions of the sex steroids with these hormones modulate the response of cartilage and bone cells to both sex steroids and the other calciotrophic hormones. These results provide the first steps towards understanding the regulation of bone cell proliferation and growth by the concerted action of a variety of hormones and growth factors.