Targeted complement inhibition and microvasculature in transplants: a therapeutic perspective.

Active complement mediators play a key role in graft-versus-host diseases, but little attention has been given to the angiogenic balance and complement modulation during allograft acceptance. The complement cascade releases the powerful proinflammatory mediators C3a and C5a anaphylatoxins, C3b, C5b opsonins and terminal membrane attack complex into tissues, which are deleterious if unchecked. Blocking complement mediators has been considered to be a promising approach in the modern drug discovery plan, and a significant number of therapeutic alternatives have been developed to dampen complement activation and protect host cells. Numerous immune cells, especially macrophages, develop both anaphylatoxin and opsonin receptors on their cell surface and their binding affects the macrophage phenotype and their angiogenic properties. This review discusses the mechanism that complement contributes to angiogenic injury, and the development of future therapeutic targets by antagonizing activated complement mediators to preserve microvasculature in rejecting the transplanted organ.

The present and future disease burden of hepatitis C virus infections with today's treatment paradigm - volume 3.

The total number, morbidity and mortality attributed to viraemic hepatitis C virus (HCV) infections change over time making it difficult to compare reported estimates from different years. Models were developed for 15 countries to quantify and characterize the viraemic population and forecast the changes in the infected population and the corresponding disease burden from 2014 to 2030. With the exception of Iceland, Iran, Latvia and Pakistan, the total number of viraemic HCV infections is expected to decline from 2014 to 2030, but the associated morbidity and mortality are expected to increase in all countries except for Japan and South Korea. In the latter two countries, mortality due to an ageing population will drive down prevalence, morbidity and mortality. On the other hand, both countries have already experienced a rapid increase in HCV-related mortality and morbidity. HCV-related morbidity and mortality are projected to increase between 2014 and 2030 in all other countries as result of an ageing HCV-infected population. Thus, although the total number of HCV countries is expected to decline in most countries studied, the associated disease burden is expected to increase. The current treatment paradigm is inadequate if large reductions in HCV-related morbidity and mortality are to be achieved.

Strategies to manage hepatitis C virus infection disease burden - volume 3.

The hepatitis C virus (HCV) epidemic was forecasted through 2030 for 15 countries in Europe, the Middle East and Asia, and the relative impact of two scenarios was considered: increased treatment efficacy while holding the annual number of treated patients constant and increased treatment efficacy and an increased annual number of treated patients. Increasing levels of diagnosis and treatment, in combination with improved treatment efficacy, were critical for achieving substantial reductions in disease burden. A 90% reduction in total HCV infections within 15 years is feasible in most countries studied, but it required a coordinated effort to introduce harm reduction programmes to reduce new infections, screening to identify those already infected and treatment with high cure rate therapies. This suggests that increased capacity for screening and treatment will be critical in many countries. Birth cohort screening is a helpful tool for maximizing resources. Among European countries, the majority of patients were born between 1940 and 1985. A wider range of birth cohorts was seen in the Middle East and Asia (between 1925 and 1995).

Historical epidemiology of hepatitis C virus (HCV) in select countries - volume 3.

Detailed, country-specific epidemiological data are needed to characterize the burden of chronic hepatitis C virus (HCV) infection around the world. With new treatment options available, policy makers and public health officials must reconsider national strategies for infection control. In this study of 15 countries, published and unpublished data on HCV prevalence, viraemia, genotype, age and gender distribution, liver transplants and diagnosis and treatment rates were gathered from the literature and validated by expert consensus in each country. Viraemic prevalence in this study ranged from 0.2% in Iran and Lebanon to 4.2% in Pakistan. The largest viraemic populations were in Pakistan (7 001 000 cases) and Indonesia (3 187 000 cases). Injection drug use (IDU) and a historically unsafe blood supply were major risk factors in most countries. Diagnosis, treatment and liver transplant rates varied widely between countries. However, comparison across countries was difficult as the number of cases changes over time. Access to reliable data on measures such as these is critical for the development of future strategies to manage the disease burden.

Complement and macrophage crosstalk during process of angiogenesis in tumor progression.

The complement system, which contains some of the most potent pro-inflammatory mediators in the tissue including the anaphylatoxins C3a and C5a are the vital parts of innate immunity. Complement activation seems to play a more critical role in tumor development, but little attention has been given to the angiogenic balance of the activated complement mediators and macrophage polarization during tumor progression. The tumor growth mainly supported by the infiltration of M2- tumor-associated macrophages, and high levels of C3a and C5a, whereas M1-macrophages contribute to immune-mediated tumor suppression. Macrophages express a cognate receptors for both C3a and C5a on their cell surface, and specific binding of C3a and C5a affects the functional modulation and angiogenic properties. Activation of complement mediators induce angiogenesis, favors an immunosuppressive microenvironment, and activate cancer-associated signaling pathways to assist chronic inflammation. In this review manuscript, we highlighted the specific roles of complement activation and macrophage polarization during uncontrolled angiogenesis in tumor progression, and therefore blocking of complement mediators would be an alternative therapeutic option for treating cancer.

Celiac disease.

Celiac disease, with a prevalence around 1% of the general population, is the most common genetically-induced food intolerance in the world. Triggered by the ingestion of gluten in genetically predisposed individuals, this enteropathy may appear at any age, and is characterized by a wide variety of clinical signs and symptoms. Among them, gastrointestinal presentations include chronic diarrhea, abdominal pain, weight loss or failure to thrive in children; but extra-intestinal manifestations are also common, and actually appear to be on the rise. They include a large variety of ailments, such as dermatitis Herpetiformis, anemia, short stature, osteoporosis, arthritis, neurologic problems, unexplained elevation of transaminases, and even female infertility. For the clinician interested in oral diseases, celiac disease can lead to delayed tooth eruption, dental enamel hypoplasia, recurrent oral aphthae. Diagnosing celiac disease requires therefore a high degree of suspicion followed by a very sensitive screening test: serum levels of the autoantibody anti-tissue transglutaminase. A positive subject will then be confirmed by an intestinal biopsy, and will then be put on a strict gluten-free diet, that in most cases will bring a marked improvement of symptoms. Newer forms of treatment which in the future will probably be available to the non-responsive patients are currently being actively pursued.

Utilization of direct oral anticoagulants in a Saudi tertiary hospital: a retrospective cohort study.

OBJECTIVE: This study aimed to assess the appropriateness of direct oral anticoagulants (DOACs) utilization in a Saudi tertiary hospital. PATIENTS AND METHODS: Adult inpatients and outpatients diagnosed with atrial fibrillation, deep vein thrombosis, or pulmonary embolism were included in a retrospective cohort study. Patients received at least one month of apixaban, rivaroxaban, or dabigatran. The duration of the study at the Armed Forces Hospital Southern Region in Khamis Mushait, Saudi Arabia, was from January 1, 2019, to December 31, 2021. The study assessed the appropriateness of DOACs dosing, initial and follow-up monitoring, the presence of clinically significant interactions, and treatment duration adherence. RESULTS: 778 patients were included in the analysis (mean age 71.34 ± 15.98 years, equal male and female representation). Rivaroxaban was administered to 40.8% of the patients, while apixaban and dabigatran were administered to 31.02% and 28.18% of the patients, respectively. The most prevalent indication for DOACs was atrial fibrillation (72.84%), followed by deep vein thrombosis and pulmonary embolism (27.16%). The most prevalent category of medication errors was inappropriate maintenance dose (41.7%), followed by inappropriate initial dose (37.97%) and lack of laboratory parameter monitoring (36.42%). 31.5 percent of the study sample lacked baseline renal functions, while 24.5% of patients lacked baseline liver functions. 115 patients (14.8%) had potential clinically significant interactions. Regarding treatment duration, 232 patients (29.8%) were improperly prescribed DOACs based on their indications. CONCLUSIONS: In a significant proportion of DOAC patients, the prescribed rational DOAC utilization parameters were not implemented. The results of the study provide specific improvement areas and objectives for Anticoagulation stewardship programs.

Physical characterization and wound healing properties of Zamzam water.

The objective of the study was to evaluate the quality of Zamzam water, holy water for Muslims and consumed for its medicinal value. The present study demonstrates the physicochemical characterization and wound healing property of Zamzam water. The physicochemical characterization of Zamzam water samples was analyzed for dissolved oxygen, pH, conductivity, total dissolved solids, redox potential, zeta potential, polydispersity index, and zeta size. The microbial quality of Zamzam water was also assessed by exposing water samples to open air. In this work, Zamzam water was also screened for the medicinal value through wound healing properties in Wistar rats. Zamzam water exhibited a unique physicochemical characterization with high levels of dissolved oxygen, zeta potential, polydispersity index, redox potential, total dissolved solids, and conductivity before exposure to open air. After open air exposure, Zamzam water resisted the growth of bacteria. The wound healing properties of Zamzam water in vivo showed a 96% of healing effect on 12th day observation. The wound healing was achieved by modulating pro-inflammatory cytokine such as interleukin -1ß (IL-1ß), interleukin-6 (IL-6), and tumor necrosis factor -α (TNF-α). Followed by the level of apoptosis markers caspase-9 and caspase-3 were reduced. The present study proved that Zamzam water is a good-quality water and showed excellent wound healing property. Therefore, Zamzam water can be used for pharmaceutical formulations.

A prospective international observational prevalence study on prone positioning of ARDS patients: the APRONET (ARDS Prone Position Network) study.

INTRODUCTION: While prone positioning (PP) has been shown to improve patient survival in moderate to severe acute respiratory distress syndrome (ARDS) patients, the rate of application of PP in clinical practice still appears low. AIM: This study aimed to determine the prevalence of use of PP in ARDS patients (primary endpoint), the physiological effects of PP, and the reasons for not using it (secondary endpoints). METHODS: The APRONET study was a prospective international 1-day prevalence study performed four times in April, July, and October 2016 and January 2017. On each study day, investigators in each ICU had to screen every patient. For patients with ARDS, use of PP, gas exchange, ventilator settings and plateau pressure (Pplat) were recorded before and at the end of the PP session. Complications of PP and reasons for not using PP were also documented. Values are presented as median (1st-3rd quartiles). RESULTS: Over the study period, 6723 patients were screened in 141 ICUs from 20 countries (77% of the ICUs were European), of whom 735 had ARDS and were analyzed. Overall 101 ARDS patients had at least one session of PP (13.7%), with no differences among the 4 study days. The rate of PP use was 5.9% (11/187), 10.3% (41/399) and 32.9% (49/149) in mild, moderate and severe ARDS, respectively (P = 0.0001). The duration of the first PP session was 18 (16-23) hours. Measured with the patient in the supine position before and at the end of the first PP session, PaO2/FIO2 increased from 101 (76-136) to 171 (118-220) mmHg (P = 0.0001) driving pressure decreased from 14 [11-17] to 13 [10-16] cmH2O (P = 0.001), and Pplat decreased from 26 [23-29] to 25 [23-28] cmH2O (P = 0.04). The most prevalent reason for not using PP (64.3%) was that hypoxemia was not considered sufficiently severe. Complications were reported in 12 patients (11.9%) in whom PP was used (pressure sores in five, hypoxemia in two, endotracheal tube-related in two ocular in two, and a transient increase in intracranial pressure in one). CONCLUSIONS: In conclusion, this prospective international prevalence study found that PP was used in 32.9% of patients with severe ARDS, and was associated with low complication rates, significant increase in oxygenation and a significant decrease in driving pressure.

Cloning and characterizing of the ovine MX1 gene promoter/enhancer region.

Ovine MX1 (MX1) is expressed in the uterus during the estrous cycle and is strongly up-regulated during early pregnancy in the uterus and peripheral blood leukocytes. In this study we cloned the MX1 gene promoter/enhancer, and tested its response to interferon tau (IFN-tau). To address the role of IFN tau in regulating MX1 expression, serial deletion mutants were prepared along with a clone that contained a full-length promoter including the two proximal ISREs but lacking an intronic ISRE site. Promoter deletions showed the two proximal ISRE sites, but not the intronic ISRE site, were required for maximal response to IFN tau. Interestingly, MX1 promoter deletion mutants revealed the presence of distal positive (-920 to -715) and negative (-715 to -437) regulatory regions. Identifying positive and negative regulatory regions in MX1 promoter will help define the complex regulation of MX1 during early pregnancy in ruminants.

Development of early choroidal neovascular membrane in a young myope after LASIK.

PURPOSE: To describe development of early choroidal neovascular membrane (CNVM) after laser-assisted in situ keratomileusis (LASIK) procedure in a young myopic patient that was successfully managed by photodynamic therapy (PDT). METHODS: A retrospective interventional case report. RESULTS: A 20-year-old woman with myopic astigmatism underwent uneventful LASIK surgery resulting in best-corrected visual acuity (BCVA) of 20/20 bilaterally. One week later, the patient presented with decreased VA in the right eye and was found to have clinical evidence of central serous chorioretinopathy (CSC). She was treated with systemic corticosteroids without any improvement. Two weeks after LASIK, the patient's VA was 20/200 and clinical evidence of early CNVM was confirmed by fluorescein angiography, indocyanine green angiography, and optical coherence tomography (OCT). PDT resulted in the regression of her CNVM with improvement in her VA and OCT findings. CONCLUSIONS: Systemic corticosteroids may enhance CNVM in patients with LASIK-induced early CNVM. PDT may be effective in the resolution of LASIK-induced CNVM.

THE USE OF NESTED-PCR TO DETECT THE PRESENCE OF PLASMODIUM IN ANOPHELES ARABIENSIS IN JAZAN REGION, SAUDI ARABIA.

The present study was carried out in 26 viJlages at two Governates (Al-Khobah, and Haroob) in Jazan Region in Southwest Saudi Arabia to identify and detect the presence of Plasmodium in Anopheles arabiensis using nested-PCR technique. An. Arabiensis was identified by PCR and it was the predominant Anopheles mosquito in all the collection sites. A total of 257 An. Arabiensis females were collected and two samples from two villages (Almuatan and Alsabkha) out of 107 (1.87%) female mosquitoes from Haroob Governorate were found positive for the sporozoites of Plasmodium falciparum. Similarly, 3 out of 150 (2%) female mosquito samples from Um-alkhameir, AL-Khobah Governorate, were also found positive. Around fourfold increase of the sporozoite rate (from 0.61 to 2.0%) in An. arabiensis in Al-Khobah Governorate has been observed compared to the previous study of 2007-2008. The wide spread of An. arabiensis in Jazan region with >90% of the malaria cases caused by P. falciparum, along with infectivity rate ranges between 1.87 to 2.0% for P. falciparum in Al-Khobah and Haroob Governorates, suggests that P. falciparumn is the most predominant malaria parasite and An. Arabiensis is a very efficient malaria vector in the region. It also suggests more in-depth researches on the ecology, behavior, and control of An. Arabiensis to promote area-specific control programs.

TSH overcomes Braf(V600E)-induced senescence to promote tumor progression via downregulation of p53 expression in papillary thyroid cancer.

The BRAF(V600E) mutation is found in approximately 40% of papillary thyroid cancers (PTC). Mice with thyroid-specific expression of Braf(V600E) (TPO-Braf(V600E)) develop PTC rapidly with high levels of serum thyroid-stimulating hormone (TSH). It is unclear to what extent the elevated TSH contributes to tumor progression. To investigate the progression of Braf(V600E)-induced PTC (BVE-PTC) under normal TSH, we transplanted BVE-PTC tumors subcutaneously into nude and TPO-Braf(WT) mice. Regression of the transplanted tumors was observed in both nude and TPO-Braf(WT) mice. They were surrounded by heavy lymphocyte infiltration and oncogene-induced senescence (OIS) was demonstrated by strong ß-gal staining and absence of Ki-67 expression. In contrast, BVE-PTC transplants continued to grow when transplanted into TPO-Braf(V600E) mice. The expression of Trp53 was increased in tumor transplants undergoing OIS. Trp53 inactivation reversed OIS and enabled tumor transplants to grow in nude mice with characteristic cell morphology of anaplastic thyroid cancer (ATC). PTC-to-ATC transformation was also observed in primary BVE-PTC tumors. ATC cells derived from Trp53 knockout tumors had increased PI3K/AKT signaling and became resistant to Braf(V600E) inhibitor PLX4720, which could be overcome by combined treatment of PI3K inhibitor LY294002 and PLX4720. In conclusion, BVE-PTC progression could be contained via p53-dependent OIS and TSH is a major disruptor of this balance. Simultaneous targeting of both MAPK and PI3K/AKT pathways offer a better therapeutic outcome against ATC. The current study reinforces the importance of rigorous control of serum TSH in PTC patients.

Incidence and severity of keratoconus in Asir province, Saudi Arabia.

AIM: To assess the incidence and associated signs and symptoms of patients with keratoconus in Asir Province, Saudi Arabia. METHODS: 125 new keratoconus patients (51 male, 74 female; mean age 18.5 (SD 3.8) years; range 8--28 years) were recruited from referrals to the department of ophthalmology, Asir Central Hospital, over a 1 year period. Age, visual acuity, and keratometry were recorded along with clinical signs and symptoms. RESULTS: The incidence of keratoconus in Asir Province is 20 cases per 100,000 population. Also, the disease severity is high, as indicated by an early mean age (17.7 (3.6) years) with advanced stage keratoconus. Visual acuity, with either spectacles or rigid contact lenses, was 6/12 or better in 98% of eyes measured. Just over half (56%) of patients had atopic ocular disease. 16% of patients had a positive family history of the disease and 16% had atopic dermatitis (eczema and/or vitiligo). CONCLUSION: The incidence and severity of keratoconus in Asir Province, Saudi Arabia, is high with an early onset and more rapid progress to the severe disease stage at a young age. This might reflect the influence of genetic and/or environmental factor(s) in the aetiology of keratoconus.

Acute coronary syndrome caused by anomalous origin of the right coronary artery from the left sinus of Valsalva.

An anomalous origin of right coronary artery from the left sinus of Valsalva is a rare congenital anomaly of the coronary arteries. We describe a 40-year-old male hypertensive and hyperlipidemic patient who presented with typical anginal pain with normal ECG and echocardiogram and abnormal exercise ECG Test Coronary angiography showed an anomalous origin of the right coronary artery from the left sinus of Valsalva, an anomaly that has been associated with angina, myocardial infarction and sudden cardiac death. The clinical profile of this congenital anomaly is also reviewed.

Benchmarking of percutaneous injuries at the Ministry of Health hospitals of Saudi Arabia in comparison with the United States hospitals participating in Exposure Prevention Information Network (EPINet™).

BACKGROUND: Exposure to blood-borne pathogens from needle-stick and sharp injuries continues to pose a significant risk to health care workers. These events are of concern because of the risk to transmit blood-borne diseases such as hepatitis B virus, hepatitis C virus, and the human immunodeficiency virus. OBJECTIVE: To benchmark different risk factors associated with needle-stick incidents among health care workers in the Ministry of Health hospitals in the Kingdom of Saudi Arabia compared to the US hospitals participating in Exposure Prevention Information Network (EPINet™). METHODS: Prospective surveillance of needle-stick and sharp incidents carried out during the year 2012 using EPINet™ ver 1.5 that provides uniform needle stick and sharp injury report form. RESULTS: The annual percutaneous incidents (PIs) rate per 100 occupied beds was 3.2 at the studied MOH hospitals. Nurses were the most affected job category by PIs (59.4%). Most PIs happened in patients' wards in the Ministry of Health hospitals (34.6%). Disposable syringes were the most common cause of PIs (47.20%). Most PIs occurred during use of the syringes (36.4%). CONCLUSION: Among health care workers, nurses and physicians appear especially at risk of exposure to PIs. Important risk factors of injuries include working in patient room, using disposable syringes, devices without safety features. Preventive strategies such as continuous training of health care workers with special emphasis on nurses and physicians, encouragement of reporting of such incidents, observation of sharp handling, their use and implementation of safety devices are warranted.

Mass gathering and globalization of respiratory pathogens during the 2013 Hajj.

Every year, more than 10 million pilgrims arrive in the Kingdom of Saudi Arabia for the Hajj or Umrah. Crowding conditions lead to high rates of respiratory infections among the pilgrims, representing a significant cause of morbidity and a major cause of hospitalization. Pre- and post-Hajj nasal specimens were prospectively obtained from a paired cohort (692 pilgrims) and from nonpaired cohorts (514 arriving and 470 departing pilgrims) from 13 countries. The countries of residence included Africa (44.2%), Asia (40.2%), the United States (8.4%) and Europe (7.2%). Nasal specimens were tested for 34 respiratory pathogens using RT-PCR. A total of 80 512 PCRs were performed. The prevalence of viruses and bacteria increased, from 7.4% and 15.4% before the Hajj to 45.4% and 31.0% after the Hajj, respectively, due to the acquisition of rhinovirus, coronaviruses (229E, HKU1, OC43), influenza A H1N1, Streptococcus pneumoniae, Haemophilus influenzae and Staphylococcus aureus. We did not identify Middle East respiratory coronavirus carriage. At arrival, the prevalence of several viruses was clearly dependent on the pilgrim's country of origin. After Hajj participation, these viruses were isolated among pilgrims from all countries, with few exceptions. No significant differences were observed between paired and nonpaired cohort results. Our results strongly suggest that, given the particularly crowded conditions during the rituals, an international mass gathering such as the Hajj may contribute to the globalization of respiratory pathogens after the cross-contamination of pilgrims harbouring pathogens that easily spread among participants. Influenza and pneumococcal vaccination, face mask use and hand hygiene should be considered in the context of the Hajj.

Impact of the Hajj on pneumococcal transmission.

Over two million Muslim pilgrims assemble annually in Mecca and Medina, Saudi Arabia, to complete the Hajj. The large number of people in a crowded environment increases the potential for pneumococcal carriage amplification. We evaluated pneumococcal carriage prevalence with four cross-sectional studies conducted at beginning-Hajj (Mecca) and end-Hajj (Mina) during 2011 and 2012. A questionnaire was administered and a nasopharyngeal swab was collected. The swab was tested for pneumococcus, serotype and antibiotic resistance. A total of 3203 subjects (1590 at beginning-Hajj and 1613 at end-Hajj) originating from 18 countries in Africa or Asia were enrolled. The overall pneumococcal carriage prevalence was 6.0%. There was an increase in carriage between beginning-Hajj and end-Hajj cohorts for: overall carriage (4.4% versus 7.5%, prevalence ratio (PR) 1.7, 95% CI 1.3-2.3), and carriage of 23-valent pneumococcal polysaccharide vaccine serotypes (2.3% versus 4.1%, PR 1.8, 95% CI 1.2-2.7), 13-valent pneumococcal conjugate vaccine (PCV) serotypes (1.1% versus 3.6%, PR 3.2, 95% CI 1.9-5.6), 10-valent PCV serotypes (0.6% versus 1.6%, PR 2.6, 95% CI 1.2-5.3), antibiotic non-susceptible isolates (2.5% versus 6.1%, PR 2.5, 95% CI 1.7-3.6) and multiple non-susceptible isolates (0.6% versus 2.2%, PR 3.8, 95% CI 1.8-7.9). Fifty-two different serotypes were identified, most commonly serotypes 3 (17%), 19F (5%) and 34 (5%). These results suggest that the Hajj may increase pneumococcal carriage-particularly conjugate vaccine serotypes and antibiotic non-susceptible strains, although the exact mechanism remains unknown. The Hajj may therefore provide a mechanism for the global distribution of pneumococci.

Longitudinal changes in bone mineral density and bone turnover in postmenopausal women with primary hyperparathyroidism.

The aims of this study were to determine 1) whether primary hyperparathyroidism (PHPT) is associated with accelerated bone loss in postmenopausal women, 2) whether bone mineral density (BMD) and bone turnover change to a similar extent with surgery and hormone replacement therapy (HRT) in these patients, and 3) whether biochemical markers of bone turnover measured at baseline can be used to predict the change in BMD in these patients after different therapies. We studied 33 postmenopausal women with PHPT; their ages at the time of study ranged from 48-80 yr (mean +/- SD, 63 +/- 10). Total body (TB), lumbar spine (LS), and femoral neck (FN) BMD and biochemical markers of bone turnover were measured at baseline and 10-30 months (19 +/- 5) after parathyroid surgery, HRT, or no treatment. BMD was measured in 33 age-matched healthy controls at baseline and at a mean of 24 months. Baseline biochemical markers of bone turnover were measured in controls. In PHPT at baseline, the mean z-score of BMD was -1.25 at TB (95% confidence interval, -1.64 to -0.86), -0.95 at LS (-1.37 to -0.53), and -1.30 at FN (-1.65 to -0.95), whereas the mean z score was 0.45 for serum carboxy-terminal propeptide of human type I procollagen (0.02-0.89), 1.05 for bone alkaline phosphatase (0.38-1.71), 2.38 for 24-h urinary excretion of cross-linked N-terminal telopeptide of type I collagen (NTx; 1.63-3.13), and 2.36 for 24-h urinary excretion of galactosyl hydroxylysine (1.97-2.74). After surgery and HRT, BMD increased and bone turnover decreased during the follow-up. In the untreated group, BMD decreased at TB and FN, and levels of bone alkaline phosphatase, NTx/creatinine, and galactosyl hydroxylysine/creatinine increased. When the rate of change in BMD (percentage per yr) was compared with that in the control group, bone gain was significant at all three skeletal sites after surgery and HRT, and bone loss was significant at TB and FN, but not at LS, in the untreated group. There was a weak, but significant, correlation between baseline urinary NTx and the change in femoral neck BMD in the untreated group (r = -0.36; P = 0.05). We conclude that untreated postmenopausal women with PHPT have low BMD resulting from accelerated bone loss at the TB and FN. Surgery and HRT both restore BMD and bone turnover toward normal in postmenopausal women with PHPT. A single measurement of bone turnover is insufficient to predict BMD changes in individual patients with PHPT.