Lupus hepatitis: a case series of 12 patients

Purpose

Several liver manifestations have been reported in systemic lupus erythematosus (SLE) and are usually non specific. We report on our experience of lupus hepatitis.

Methods

A retrospective monocenter study of 73 patients with SLE. The diagnosis of lupus hepatitis was established after exclusion of other causes of hepatitis and hepatic vein thrombosis.

Results

Liver involvement was noted in 12 patients (16.4%). There were nine female and three male patients; the mean age of these patients was 29 years. In seven patients liver involvement was concurrent with the diagnosis of SLE and it occurred later during an exacerbation of the disease in the five remaining patients. In all patients, liver manifestations were associated with other organ involvement. Clinical manifestations were: hepatomegaly (n = 4), jaundice (n = 4), abdominal pain (n = 3), ascitis (n = 2), portal hypertension (n = 1) and hepatic failure with encephalopathy (n = 1). Elevated liver enzyme was noted in 11 cases and liver cholestasis in eight cases. Presence of anti-ribosomal P antibodies was noted in one case. Liver biopsy was performed in five patients, and revealed chronic active hepatitis in three cases, chronic hepatic granulomas in one case and nonspecific inflammation in one case. The outcome was favorable in 11 patients without relapse, and one patient died of encephalopathy and liver failure.

Conclusion

Liver involvement associated with SLE is not uncommon. It is frequently asymptomatic and limited to liver test abnormalities. The role of anti-ribosomal P autoantibodies remains uncertain.     

Observance médicamenteuse chez un échantillon d’hypertendus dans la région de Sfax (Tunisie)

The aim of the study

Medication noncompliance is one of the daily problems of the physician. Improving the medication adherence allows better management of hypertension. The aim of this work was to determine the level of compliance for patients with hypertension and to identify factors that determine compliance.

Methods

A cross-sectional study was carried out among a sample of hypertensive patients attending general and specialist practitioners in public or private clinics of Sfax. Two hundred and seventy-three participants had accepted to be interviewed. Patients were identified as noncompliants using a questionnaire developed by the Comité de lutte contre l’hypertension artérielle (CFLHTA).

Results

Non-compliance rate was 63.4%. The low level of education was associated with a lower adherence. The monotherapy, the once-daily regimen with fewer number of tablets were associated with a better adherence (p < 10⁻⁶). The welcome and the availability of drugs in the public clinic affect positively the adherence of patients (p < 0.0002). A patient very satisfied with his consultation and the explanation given by the doctor about his illness and its treatment had a better adherence (p < 0.00003).

Conclusion

Our study had demonstrated a low compliance with antihypertensive drug therapy. Tunisian health care system should elaborate a management plan which takes into account our particular predictors of compliance to improve adherence to antihypertensive medication.     

Altération de la variabilité sinusale chez les malades en hémodialyse chronique

Background and aim

Decrease in heart rate variability (HRV) is a known risk factor for cardiovascular morbidity and mortality. The aim of our study is to evaluate HRV in chronic hemodialysis patients and to determine factors that might decrease or increase it.

Methods

This is a retrospective study including 51 patients, 23 males and 28 females, with a mean of age of 64.5 years (23-84 years) on chronic hemodialysis for end stage renal disease due to various causes. Twenty-four-hour heart rate monitoring was recorded in all patients to evaluate HRV. HRV of hemodialysis patients was compared to normal patients (control). We also looked for correlation between HRV and a number of clinical and biological factors.

Results

All HRV parameters were decreased in chronic hemodialysis patients compared to normal controls with a significant difference (p < 0.0005). HRV decreases with age (p = 0.012), and is lower in diabetic patients (p = 0.026). Interestingly, we found that chronic hemodialysis patients on beta-blockers had higher HRV with p = 0.011.

Conclusion

HRV is reduced in chronic hemodialysis patients mainly in old and diabetic patients, but this decrease is less important in those receiving beta-blockers.     

Aerobic and resistance training effects compared to aerobic training alone in obese type 2 diabetic patients on diet treatment

Aims

The study was designed to compare a combined aerobic and resistance training (ART) with an aerobic training (AT) over hemodynamic, glucose metabolism and endothelial factors, adipokines and pro-inflammatory marker release in a population of obese type 2 diabetic patients.

Methods

Forty-seven patients were randomly assigned to aerobic (27 patients) or aerobic plus resistance (20 patients) exercise trainings, on the top of a diet regime. Anthropometric, metabolic, hormonal and inflammatory variables were measured at hospitalization and discharge.

Results

Both exercise programs equally improved body weight and fructosamine levels however ART only partially decreased HOMA index compared with AT (ART: −25% vs AT: −54%, p < 0.01). Mean blood pressure (AT: −3.6 mmHg vs ART: +0.6 mmHg, p < 0.05) and endothelin-1 (ET-1) incremental areas during walking test (AT: −11% vs ART: +30%, p < 0.001) decreased after AT while increased after ART. Adiponectin levels increased by 54% after AT while decreased by 13% after ART (p < 0.0001) and matrix metalloproteinase-2 (MMP-2), tumor necrosis factor-alpha (TNF-alpha) and monocyte chemoattractan protein-1 (MCP-1) levels significantly decreased in AT while increased in ART group.

Conclusions

Compared with AT, ART similarly enhanced body weight loss but exerted less positive effects on insulin sensitivity and endothelial factors, adipokines and pro-inflammatory marker release.     

Association of eNOS gene polymorphisms with renal disease in Caucasians with type 2 diabetes

Aim

In this study we investigated if the −786T > C, the VNTR intron 4 a/b and the 894G > T (Glu298Asp) polymorphisms in the eNOS gene were associated with renal disease in 617 type 2 diabetic Caucasian-Brazilians. These polymorphisms were also examined in 100 Caucasian healthy blood donors.

Methods

Genotyping of eNOS polymorphisms was performed by PCR or PCR-RFLP and haplotype frequencies were estimated using a Bayesian method. Logistic regression analysis was done to test for association of eNOS polymorphisms with susceptibility to renal involvement (microalbuminuria, macroalbuminuria or end-stage renal disease). This analysis was carried out assuming three diferent genetic models for the minor allele, adjusting for possible effect modifiers.

Results

Genotype and allele frequencies in patients with renal disease were not significantly different from those of patients with normoalbuminuria and healthy blood donors for all eNOS polymorphisms. Likewise, there were no differences in haplotype frequencies among healthy blood donors and type 2 diabetic patients with or without renal involvement (P > 0.05 for all comparisons).

Conclusion

No associations between the −786T > C, the VNTR intron 4 a/b and the 894G > T (Glu298Asp) polymorphisms in the eNOS gene and renal disease were observed in type 2 diabetic Caucasian-Brazilians.     

Approche multifactorielle et typologique du concept de fragilité chez les patients hypertendus non contrôlés. Enquête Eclat

Objective

The aim of the Eclat survey was to evaluate the frequency of frailty in uncontrolled hypertensives and to individualize different frailty profiles.

Patients and methods

This was an observational, prospective, longitudinal survey conducted in the cohort of uncontrolled hypertensive patients aged 55 years or more. Morbid events having occurred between two visits at a 6-month interval were reported. Patients with at least one event were considered to be frail. Predictive factors of at least one event were identified (logistic regression). The analysis was completed by a typological analysis (principal components analysis and clustering).

Results

At least one event occurred in 211 (9%) of 2306 patients (males 55%, 67 ± 9 years old, blood pressure [BP] = 160 ± 11/93 ± 8 mmHg, diabetes 23%): cardiovascular (1.7%), gerontological (5.5%), onset of diabetes (1.3%), worsening of renal impact (2%). Three frailty profiles were identified: patients at low risk (n = 1507, event rate = 6%), with neither cardiovascular risk factors nor target organ damage; patients at moderate risk (n = 335, event rate = 12%) with numerous risk factors but no target organ damage and patients at high risk (n = 243, event rate = 23%), the older ones, in bad general condition, with target organ damage, sensorial deficits and cognitive disorders. In a population of uncontrolled hypertensives aged 55 years or more, 9% could be considered as frailty.

Conclusion

Therapeutic measures might be adapted according to the frailty profile of the patient. With respect to treatment management, healthcare behaviour could differ depending on these frailty profiles.     

A qualitative examination of patient awareness and understanding of type 2 diabetes and oral health care needs

Aims

The study examined awareness and understanding of the bidirectional relationship between type 2 diabetes and oral health care in adult patients with type 2 diabetes.

Methods

Focus groups were held with 30 participants with type 2 diabetes. Groups were comprised of African Americans (n = 16), Hispanics (n = 6), and Caucasians (n = 8). A grounded theory approach was used to analyse and interpret findings.

Results

Participants were unaware of the relationship between type 2 diabetes and oral health but were concerned about the influence of poor oral health on quality of life. Having diabetes was reported as a potential challenge for the coordination and receipt of dental care. Patient-provider communication of diabetes and oral health needs were perceived to be inadequate.

Conclusions

Patients with type 2 diabetes are at-risk for poor oral health, yet have limited awareness and understanding of the specific oral health care needs and risks associated with type 2 diabetes. This lack of awareness and understanding of the relationship between diabetes and oral health may be an indicator of inadequate oral health literacy. Addressing the relationship between diabetes and oral health with patients may improve dental outcomes, increase quality of life, and promote oral health literacy in at-risk populations.     

Type 2 diabetes and universal health care for low-income groups: a case-control study

Purpose

In 2007 in France, type 2 diabetes involved 2.5 million people, and 4.5 million patients received free healthcare coverage under the universal healthcare coverage program (CMU) for low-income households. An optimal glycemic control and adequate diabetes monitoring can reduce the incidence of complications. The objective of this study was to compare the diabetes care of low-income patients (as defined by CMU coverage) with the rest of the population.

Methods

A retrospective case-control study (non-CMU and CMU) over a one-year period of glycemic control for both populations through private laboratory data (number and values of HbA1c) and of individuals monitoring through data from the regional health insurance public institute.

Results

Regarding glycemic control, 154 patients were included. The number of annual HbA1c tests was similar between CMU and non-CMU patients. The mean HbA1c value was higher for CMU patients (8.7% versus 8%; P < 0.01). Regarding monitoring, 1254 patients were included. Over a one-year period, the number of HbA1c tests, lipid profile tests, serum creatinine measures and cardiology consultations were similar across groups. However, CMU patients benefited from less microalbuminuria testing (P < 0.001), ophthalmologic monitoring visits (P < 0.01), endocrinology consultations (P < 0.01), and from more general physician consultations (P < 0.001).

Conclusions

Receiving CMU health coverage was associated with a poorer glycemic control and lesser specialized monitoring than that was observed in control patients. Across the population, follow-up recommendations are far from being implemented satisfactorily.     

Potential celiac disease in type 1 diabetes: a multicenter study

Aims

To describe the prevalence of potential celiac disease (pot-CD) in young patients with type 1 diabetes mellitus (T1DM) and characterize their clinical features.

Methods

This cross-sectional multicenter study involved 8717 T1DM patients from 31 Italian centers. Information was collected on the total number of T1DM patients, CD patients and pot-CD patients. The following data were collected on pot-CD patients: gender, age at T1DM diagnosis, age at the first CD serological positivity, presence of CD-related symptoms, presence of other autoimmune disorders and treatment with gluten free diet (GFD). One thousand-three-hundred-sixty-one patients who were positive for CD serology were the control group.

Results

CD serological positivity was found in 7.2% T1DM patients. Prevalence of pot-CD was 12.2% (n = 77) among CD positive patients: symptoms were present in 12/77; a third autoimmune disorder was found in 15 patients. Prevalence of pot-CD in the control population was 8.4% (n = 114; p = 0.005). No difference was found with regard to clinical features. Only few symptomatic patients were on GFD both in T1DM and control patients.

Conclusions

A higher prevalence of pot-CD was found in T1DM patients, that may be ascribed to the routine screening, although the influence of genetic factors cannot be excluded.     

Nasosinusal and cervical sarcoidosis: a case series of three patients and literature review

Introduction

Sinonasal sarcoidosis is difficult to treat. Infliximab seems to be useful in the treatment of sarcoidosis of the upper respiratory tract.

Case series

We report three cases of sinonasal sarcoidosis in two women of 36 and 42-year-old and in a 64-year-old man. Resistance or dependence to corticosteroids and absence of efficacy of methotrexate therapy in one patient led to administer anti-TNFα therapy with infliximab. Outcome was favourable on sarcoid lesions but treatment was discontinued because of infectious complications and worsening of sarcoid chest involvement.

Conclusion

This case series suggests that infliximab might be useful for the treatment of sarcoidosis with sinonasal involvement.     

Oral anticoagulation doesn't increase hemorrhagic risk in patients undergoing a cardiac pacemaker or defibrillator implantation

Objectives

This study was designed to assess the hypothesis that the implantation or the replacement of a cardiac stimulator or defibrillator in patients receiving oral anticoagulants with an INR ≥ 2 doesn’t increase the hemorrhagic risk in comparison with patients for whom the treatment has been interrupted temporarily (INR < 2) or with patients not receiving anticoagulants (control group).

Patients and results

We performed a retrospective chart review of bleeding complications in all patients undergoing pacemaker or ICD implantation or replacement between January 2007 and may 2009. In this cohort, 43 patients (10%) were implanted with an INR ≥ 2 while 36 patients (8%) were implanted with an INR < 2 and 352 patients (82%) didn’t receive anticoagulants. No complication (0/36) has been observed in patients having an INR < 2, while 3/43 (7%) complications have been observed in patients with an INR ≥ 2 and 13/352 (3.7%) in patients in the control group (p = 0.3093). Duration of the hospital stay was similar in the three groups: 6.2 days in patients with an INR < 2, 6.8 days in the group with an INR ≥ 2 and 6.2 days in the control group (p = 0.686).

Conclusion

Pacemaker and ICD implantation or replacement without withdrawing of oral anticoagulants and an INR ≥ 2 was not associated with an increase of the hemorrhagic risk.     

Uvéites révélant une sarcoïdose : caractéristiques cliniques à propos de 23 cas

Purpose

Uveitis may rarely reveal sarcoidosis in Caucasian patients. Our objective was to analyze the clinical manifestations, and the outcome in a group of patients in whom uveitis was the presenting manifestation of sarcoidosis.

Methods

Retrospective study including 23 patients (mean age: 50.3 ± 14.5 years) diagnosed with sarcoidosis after an episode of uveitis. Granulomatous lesions were documented in 14 patients.

Results

Ophthalmological examination revealed anterior uveitis (n = 5), intermediate uveitis (n = 2), posterior uveitis (n = 25) and panuveitis (n = 11). Ocular inflammation was bilateral in 16 patients (69,6%), typical aspects of granulomatous uveitis were found in only 16 eyes over 39 (41%), posterior uveitis was found in 18 eyes (46.2%), with an averaged visual acuity of 5/10. Macular oedema was noted in five patients. Suggestive signs of ocular sarcoidosis were present in 43% of the patients. Stage 1 or 2 pulmonary involvement (n = 22), musculoskeletal (22%), skin (13%), or spleen (9%) involvements were the most common findings. Oral corticosteroids were necessary in 91.3% of the patients, immunosuppressive agents in 26.1%, with a prolonged treatment greater than two years in 58%. The visual prognosis was good, with visual acuity greater than 6/10 in 96% of the cases if the ocular inflammation spared retina and choroid. However, a visual acuity less than 6/10 was observed in 44% of the cases when the posterior segment was involved.

Conclusion

Sarcoidosis may be revealed by an intraocular inflammation, with typical patterns in only 43% of the cases. Sarcoidosis should therefore be included in the differential diagnosis of every uveitis. Oral corticosteroids are required in almost all cases, owing to ocular involvement rather than visceral involvement.     

Hyperuricemia in sickle cell disease in France

Purpose

Hyperuricemia has been reported to be a common feature of sickle cell disease occurring between 32 to 41% of the patients, in studies conducted during the 1970's. Since then, this notion has been rarely challenged. The objective of this study was to assess the prevalence of hyperuricemia and gout in adult patients with sickle cell disease in France.

Methods

Between May 2007 and March 2009, serum and urinary urate concentration, creatininemia and hemogram were prospectively assessed in all consecutive sickle cell patients, followed in our sickle cell disease centre. All subjects were in a clinically steady state. Clinical acute gout history was also recorded.

Results

Sixty-five patients (mean age 31 ± 10.3 years) were investigated. Mean uric acid serum level was 281.6 ± 74 μmol/L. Hyperuricemia was evidenced in six patients only (9.2%) (95% IC: 3.5-19.0). None of the patient had a medical history of acute gout. Patients in the higher serum uric acid tertile concentration had higher serum creatinine level (62.3 ± 17.1 μmol/L vs 51.5 ± 12.6 μmol/L, P < 0.01), lower fractional excretion of urate (4.5% vs 6.8%, P < 0.03) and higher reticulocyte count (median 219 500/mm³ vs 144 000/mm³, P = 0.08) compared to the other patients.

Conclusion

Hyperuricemia and gout are not a clinical problem in sickle cell disease in our country. Nevertheless, our findings indicate that kidney function has to be fully explored if serum uric acid level is elevated or significantly deteriorates during follow-up. Serum uric acid level could be an early marker of renal dysfunction in sickle cell disease patients.     

Serum asymmetric dimethylarginine levels in diabetic patients with neuropathy

Objective

The goal of our study was to evaluate the role of asymmetric dimethylarginine (ADMA) in patients with diabetic neuropathy.

Materials and methods

In this study, 58 diabetic patients and 26 healthy volunteers were included. In both groups ADMA measurements were performed together with other biochemical examinations. Nerve conduction studies and Neuropathy Symptom Score (NSS) were administered to the diabetic patients.

Results

ADMA levels were found significantly higher in diabetic patients compared to the control group (p = 0.0001). However, ADMA levels were not statistically significant between diabetic patients with neuropathy and without neuropathy (p = 0.86 and p = 0.47).

Conclusion

These results demonstrate that there is not any significant relationship between ADMA and diabetic neuropathy.     

Valeur prédictive comparée de mortalité hospitalière du peptide natriurétique de type B et de l’albuminémie chez le sujet âgé hospitalisé pour insuffisance cardiaque aiguë sévère

Objective

To address the clinical relevance of serum albumin and B-type natriuretic peptide (BNP) concentration in the prediction of in-hospital death in elderly patients with acute severe heart failure.

Patients and methods

Seventy-four consecutive patients >70 years of age admitted for acute heart failure in NYHA class IV were prospectively included. BNP concentration was measured on admission and serum albumin concentration after clinical stabilization.

Results

Mean age was 86.6 ± 5.7 years. Sixty-five percent of patients had a normal left ventricular ejection fraction. Eighteen patients died during the in-hospital stay. Those patients who died were older, had higher blood urea nitrogen and BNP concentration, had lower systolic blood pressure and serum albumin concentration than patients who survived. Heart rate, rhythm, left ventricular ejection fraction, serum creatinine and hemoglobin did not differ according to outcome. By multivariate analysis, albumin (p = 0.0017), BNP (p = 0.016) and age (p = 0.03) were independent predictors of in-hospital death. Serum troponin I measured on admission in 71 patients was predictive of in-hospital death (p = 0.01), as well as serum total cholesterol measured after stabilization in 66 patients (p = 0.004). However, these two variables no longer predicted outcome in multivariate models, unlike serum albumin and BNP.

Conclusion

Serum albumin and BNP offer independent, additional information for the prediction of in-hospital death in elderly patient with acute severe heart failure regardless of left ventricular ejection fraction.     

Screening for Obstructive Sleep Apnea on the Internet: Randomized Trial

Background

Obstructive sleep apnea is underdiagnosed. We conducted a pilot randomized controlled trial of an online intervention to promote obstructive sleep apnea screening among members of an Internet weight-loss community.

Methods

Members of an Internet weight-loss community who have never been diagnosed with obstructive sleep apnea or discussed the condition with their healthcare provider were randomized to intervention (online risk assessment + feedback) or control. The primary outcome was discussing obstructive sleep apnea with a healthcare provider at 12 weeks.

Results

Of 4700 members who were sent e-mail study announcements, 168 (97% were female, age 39.5 years [standard deviation 11.7], body mass index 30.3 [standard deviation 7.8]) were randomized to intervention (n = 84) or control (n = 84). Of 82 intervention subjects who completed the risk assessment, 50 (61%) were low risk and 32 (39%) were high risk for obstructive sleep apnea. Intervention subjects were more likely than control subjects to discuss obstructive sleep apnea with their healthcare provider within 12 weeks (11% [9/84] vs 2% [2/84]; P = .02; relative risk = 4.50; 95% confidence interval, 1.002-20.21). The number needed to treat was 12. High-risk intervention subjects were more likely than control subjects to discuss obstructive sleep apnea with their healthcare provider (19% [6/32] vs 2% [2/84]; P = .004; relative risk = 7.88; 95% confidence interval, 1.68-37.02). One high-risk intervention subject started treatment for obstructive sleep apnea.

Conclusion

An online screening intervention is feasible and likely effective in encouraging members of an Internet weight-loss community to discuss obstructive sleep apnea with their healthcare provider.     

Extensive iatrogenic coronary dissection during coronary angioplasty: a series of 19 consecutive patients

Purpose of the study

Extensive coronary dissection is a rare complication of intraluminal angioplasty. We report a retrospective study of 19 patients who consulted in a general hospital without cardiac surgery.

Patients and methods

After consulting our coronarography and angioplasty database, we included the extensive coronary dissections (type D, E and F) in our study. The medical files of the selected patients were analysed.

Results

Between January 2003 and March 2010, 19 coronary angioplasty (total: 2542) were complicated with extensive dissections (incidence 0,75%). For 62,3% of the patients, the dissection was related to the guiding catheter. Eleven patients had type A and B1 lesions. The dissections affected the right coronary artery for 16 patients, the left anterior descending coronary artery for two patients and the left main coronary artery for one patient. After angioplasty, a final TIMI flow 3 was obtained for only 11 patients. In nine cases, we observed a limited extension to the aorta that did not need a chirurgical intervention and had no influence on the prognosis. The complications were common, such as death (n = 1), coronary bypass (n = 2), myocardial infarction (n = 8), cardiogenic shock (n = 2) and circulatory assistance (n = 2).

Conclusion

Extensive coronary dissection is a rare complication of angioplasty. The right coronary is the most frequent vessel concerned and an extension to aorta is usual. The treatment is usually based on sealing the entry with a coronary stent. The complications are common and serious and we did not find any predicting factors to extensive coronary dissections that are unpredictable.     

Serotonin levels in platelet-poor plasma and whole blood in people with type 2 diabetes with chronic kidney disease

Aims

Patients with diabetes mellitus (DM) are prone to atherosclerosis. Atherosclerosis activates platelets; activated platelets release serotonin, and therefore, evaluation of serotonin levels in blood could be a valuable biomarker for future risk of cardiovascular events.

Methods

Plasma serotonin levels obtained from patients with DM complicated with chronic kidney disease were measured using HPLC and were compared to serotonin levels of healthy control subjects. Patients with DM were classified into 2 subgroups of mildly (group 1) and moderately/severely (group 2) impaired renal function.

Results

Serotonin concentration in platelet-poor plasma for group 1 was significantly higher than that of healthy control subjects (p < 0.01), and was significantly higher than that of patients from group 2 (p < 0.05). The concentration of serotonin in whole blood for group 2 patients was significantly lower than that measured from healthy control subjects (p < 0.01). The ratio of the plasma to whole blood level was significantly elevated in both groups 1 and 2 compared with healthy controls (p < 0.01).

Conclusions

Our results indicate that platelets are activated to release serotonin into plasma in diabetic patients with mildly impaired renal function. When renal damage is advanced, platelets are over-activated to release serotonin.     

The foot in type 2 diabetes: is there a link between vascular calcification and bone mineral density?

Aims

To examine the relationship between vascular calcification in the foot (FVC) and bone mineral density (BMD) in the heel of type 2 diabetes mellitus (DM) subjects.

Methods

65 subjects with type 2 DM and serum creatinine < 125 μmol/l underwent CT scanning of the foot to assess FVC and dual energy X ray absorptiometry (DEXA) scan to assess heel BMD. Routine biochemistry including osteoprotegerin (OPG) and Receptor activator of nuclear factor kappa-B ligand (RANKL) was also carried out.

Results

The proportion of subjects with FVC was 43%, whilst 40% had low BMD (T score < −1.0). Age, neuropathy and 25 hydroxyvitamin D were independent predictors of FVC. Body-weight, eGFR, 25 hydroxyvitamin D, OPG, and total cholesterol were independent predictors of low heel BMD. There was no correlation between albuminuria and BMD or FVC. There was no difference in heel BMD between those with FVC and those without, but those with frank osteoporosis were significantly more likely to have FVC than those with higher BMD.

Conclusions

There is no clear-cut association between FVC and low BMD in type 2 DM with relatively well-preserved renal function. Age, neuropathy, eGFR, hyperlipidemia, body-weight, 25 hydroxyvitamin D and OPG play a complex role in their pathogenesis.