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Inflammatory bowel disease in Thai children: presentations and outcomes of treatment.

Inflammatory bowel disease (IBD) is characterized by idiopathic chronic intestinal inflammation, due to abnormalities in gastrointestinal immunoregulation. Pediatric IBD has been rarely reported in Thailand. We describe eight children, five girls and three boys, who were diagnosed with IBD at Ramathibodi Hospital during 1999-2005 and had a follow-up of more than one year. Four cases had Crohn's disease (CD) and four cases had ulcerative colitis (UC). The ages at diagnosis ranged from 3.5 to 15.5 years. Diagnosis of IBD was delayed for more than 12 months in five patients. Five out of eight patients had early onset of disease, before 6 years of age. The manifestations included chronic diarrhea, abdominal pain, rectal bleeding and perianal lesions. The common extraintestinal manifestations were oral ulcer, anemia, weight loss and failure to thrive. Most patients had moderate to severe diseases and ileocolic fistula developed in one patient with CD. The disease was controlled with 5-aminosalicylic acid and corticosteroid in most patients. Four patients required additional therapy with azathioprine. Infliximab was used in two patients who were chronically steroid-dependent CD, one also had persistent ileocolic fistula and both patients responded well. During the follow-up period ranging from 1.1 to 5.8 years, three patients remained growth retardation; all had early onset of disease before 6 years of age, long duration of symptoms of more than 3 years before diagnosis and had multiple relapses. It is concluded that there is an increasing number of IBD in Thai children during the recent years. Most patients had moderate to severe diseases. Early onset of disease, delay in diagnosis and treatment are responsible for more complications, particularly persistent growth impairment. Early recognition of IBD and treatment are essential for a satisfactory long-term outcome.

Adolescent↗

Epidemiology of inflammatory bowel disease over a 10-year period in Florence (1978-1987).

The epidemiology of inflammatory bowel disease (IBD) in southern Europe is still not well-known. Sporadic reports have suggested a lower incidence and a milder course of the disease in Italy, but conclusive data are still lacking. To shed light on this issue, we conducted a retrospective study of IBD incidence (from January 1978 to December 1987) in the metropolitan area of Florence (650,000 inhabitants). We also estimated IBD prevalence at December 31, 1987. Our study included both in-patients and out-patients referred to the Gastroenterological and Surgical Departments of the area. The diagnosis was based on well-established clinical, endoscopical, radiological, histological and surgical criteria. Overall, nine-hundred IBD patients were identified, but only 359 (195 males, 164 females) met the eligibility criteria for inclusion in the incidence study (area of residence and period of diagnosis); of these, 263 had ulcerative colitis (UC), 96 had Crohn's disease (CD), and 6 had IBD. The average incidence rate of CD was 1.5/100,000 per year while its prevalence was 17.3/100,000. The average incidence rate of UC was 4.0/100,000 per year and the prevalence was 49.6/100,000. Both the incidence and the prevalence rates for UC and CD were higher in males than in females. This retrospective, hospital-based study shows that, in this area, the incidence rate of IBD has steadily increased over the period considered. Further studies specifically focused on risk factors are needed.

Adult↗

Standard requirements for vaccines against infectious bursal disease.

A variety of criteria must be considered when examining the suitability of preparations of live infectious bursal disease (IBD) virus for use as vaccines: identity and purity of the vaccine strain, lack of spread, or of tendency to revert to virulence, lack of immunosuppressive effect, safety and potency. Arguments as to th identity of IBD virus are well documented, and after ensuring that the virus strain is in fact IBD virus, it must be ascertained that it is free from contaminating agents. If the vaccine strain spreads, lack of reversion to virulence must be determined by several direct chick to chick passages: histological observations of bursae from first and final passages must be made to ensure that no change has occurred. In order to formulate proposals for standard tests of safety, lack of immunosuppressive effect and potency for IBD vaccines, comparative studies were made of products of different origins. Safety of the vaccines was assessed by observing young chicks after administration and measuring loss in weight gain. The effect on the bursa was judged by weighing and making microscopic observations at intervals. The immunosuppressive effect of the vaccines was assessed by comparing the serological and protective responses to subsequent Newcastle disease (ND) vaccination with the response in chicks given no IBD vaccine. Potency of the vaccines was determined by challenge of vaccinated chicks with virulent IBD virus. Various properties were found in the products examined. Some were concluded to be insufficiently attenuated because of the effect on the bird or upon its bursa and the consequent effect on the bird's immune competence. The ability to confer protection was not correlated with the degree of damage caused in the bursa. Vaccines which had no adverse effect on the health of the bird, caused little or no damage to the bursa and conferred adequate protection against challenge were considered to be of a satisfactory standard.

Animals↗

Smoking and inflammatory bowel disease in families.

Smoking habits of inflammatory bowel disease (IBD) patients were compared with family members with IBD to determine the effects of cigarette smoking on the development of either ulcerative colitis or Crohn's disease. In a previous study of patients randomly selected from the University of Chicago IBD Registry, 40 patients with IBD were identified as having a confirmed IBD family history. Thirty-one of those probands and relatives were contacted and included in this study. Of the 36 patients in the study with Crohn's disease, 78% were former or current smokers, whereas only 27% of the 26 patients with ulcerative colitis were former or current smokers. Eighty-three percent of all those who had ever smoked, started before the onset of symptoms of their disease. There were high concordance rates for type of IBD (81%) and for smoking habits (65%, when a history of smoking was compared with a history of never having smoked) among the matched pairs. The concordance rates were not significantly different from each other, but the magnitude of concordance of each suggests that both smoking habits and consanguinity may be important factors in the pathogenesis of this disease.

Adult↗

Serum IgE levels in patients with inflammatory bowel disease.

The role of allergy in the pathogenesis of inflammatory bowel disease (IBD) is unclear. The present study was performed to evaluate serum levels of IgE and other immunoglobulin classes in patients with IBD. Patients with IBD had significantly elevated serum levels of both IgG and IgM in the presence of normal levels of IgA. Serum concentration of IgE, as well as the prevalence of patients with "high IgE" were significantly increased in IBD. Among patients with IBD, those with Crohn's disease or those in relapse had the highest levels of IgE. The possibility that allergy plays a pathogenic role in a subset of IBD is discussed.

Adolescent↗

Secretory immunoglobulin deficiency in a family with inflammatory bowel disease.

A family with 4 of 10 first-degree relatives affected with inflammatory bowel disease (IBD) was studied to determine whether any distinct immunological abnormalities occur in the affected members, as compared with unaffected members of the family, normal controls, and other unrelated patients with IBD. Red cell blood type and HL-A phenotypes did not distinguish between healthy and affected members, although HL-A2, 32, B27, and B12 were the predominant haplotypes in members with IBD. There was no significant difference between the two groups in the lymphocyte subpopulation counts of T cells, B cells, and cells carrying Fc or complement receptors. The in vitro mitogen response, however, to phytohemagglutinin and pokeweed mitogen were depressed in the affected members. Serum IgA and C3 levels were significantly elevated in members with IBD compared to healthy subjects with values of 232 +/- 69 (mean +/- SD) versus 148 +/- 29 mg per dl for IgA (P less than 0.05) and 173 +/- 32 versus 115 +/- 22 mg per dl for C3 (P less than 0.025), respectively. Plasma and, to a lesser extent, peripheral lymphocytes from 2 affected members who were tested were cytotoxic to allogeneic colonic epithelial cells. Salivary IgA was normal in the affected family members and unrelated patients with IBD. However, the free secretory component of salivary IgA was absent or markedly depressed in family members, as well as in unrelated patients with ulcerative colitis. This deficiency of the secretory immune system appears to characterize more frequently ulcerative colitis than Crohn's disease and may compromise mucosal host defenses in IBD.

Adolescent↗

Colo-rectal biopsy in inflammatory bowel disease.

The term inflammatory bowel disease (IBD) is viewed as all-inclusive, covering the full panoply of intestinal disorders in which inflammatory changes are a prominent feature, including those of infectious, toxic, and intrinsic origin as well as the idiopathic entities ulcerative colitis and Crohn's disease. This chapter describes and discusses those aspects of colo-rectal biopsy in IBD which can help pathologists make optimal interpretations. The areas covered are: 1) methods used to prepare biopsy specimens for study, 2) normal histologic findings and common artefacts, 3) basic pathologic changes occurring in IBD, 4) a general approach to differential diagnosis in IBD, and 5) discussion of the various individual forms of IBD. The importance of full and reliable information exchange between the endoscopist and pathologist is stressed. Special attention is given to features in biopsy specimens which help in differentiating between ulcerative colitis and Crohn's disease. Other entities discussed are bacterial dysenteries; gonococcal proctitis; tuberculosis; Whipple's disease; amebiasis; balantidiasis; schistosomiasis; cryptosporidiosis; lymphopathia venereum; cytomegalovirus infection; histoplasmosis; antibiotic colitis; IBD due to cytotoxic drugs (5-FU), heavy metals, and foodstuffs; irradiation colitis; ischemic colitis; solitary ulcer syndrome; diverticulitis; and colitis secondary to obstruction. The term pseudomembranous enterocolitis is also considered.

Biopsy↗

Effect of infectious bursal disease virus infection on the phagocytosis of Staphylococcus aureus by mononuclear phagocytic cells of susceptible and resistant strains of chickens.

Studies were conducted to determine why chickens infected with infectious bursal disease (IBD) are more susceptible to Staphylococcus aureus. We evaluated the effect of IBD virus on functions of the peripheral mononuclear phagocytes and looked for humoral abnormalities in the serum. An in vitro opsonophagocytic assay using (H3) thymidine-labeled opsonized Staphylococcus aureus was used to measure phagocytosis. Infection of IBD-sensitive (SCWL 420) chickens with IBD virus did not cause any cellular defects, as shown by phagocytic inability, or any humoral abnormalities, as shown by the lack of opsonics. However, IBD virus did cause some humoral defects 2 weeks postinfection in resistant (Hardy Red) chickens. Therefore, the basic mechanisms governing increased susceptibility of IBD-infected chickens to S. aureus is still unknown.

Animals↗

Decreased incorporation of 14C-glucosamine relative to 3H-N-acetyl glucosamine in the intestinal mucosa of patients with inflammatory bowel disease.

The synthesis of glycoproteins was investigated in intestinal mucosa from patients with inflammatory bowel disease (IBD) and from those with various other conditions. The incorporation into acid-insoluble macromolecules of the amino sugar glucosamine, the first and committed metabolite in the biosynthetic sequence, and its immediate derivative, N-acetyl glucosamine was determined. Tissue was incubated with 1-2 nmol 14C-glucosamine and 3H-N-acetyl glucosamine and the simultaneous incorporation of both isotopes was measured. Bowel tissue from areas microscopically uninvolved in active disease process was examined. Values for the incorporation of both substrates into acid-soluble constituents were similar for both IBD and non-IBD groups, as was also the incorporation of 3H into acid-insoluble constituents. The incorporation of 14C, however, when expressed relative to that of 3H in each individual patient, i.e., 14C/3H, was distinctly different in IBD cases. In 26 non-IBD samples this ratio ranged from 0.04-0.26 with a mean of 0.097 +/- 0.009. In nine cases of Crohn's disease values ranged from 0.013-0.06 with a mean of 0.039 +/- 0.011 (p less than 0.01); in nine cases of ulcerative colitis values were 0.007-0.06 with a mean of 0.031 +/- 0.006 (p less than 0.01). It is concluded that the step involving the N-acetylation of the amino sugar is relatively deficient in patients with IBD and this could reduce the synthesis of the glycoprotein cover which protects the mucosa from damage by bowel contents.

Acetylglucosamine↗

Thyroid involvement in patients with active inflammatory bowel diseases.

Previous studies have documented an association between systemic diseases and disorders of the thyroid gland, expressed by an enlargement of the thyroid and by the presence of anti-thyroid antibodies. Chronic inflammatory bowel diseases (IBD, ulcerative colitis and Crohn's disease) may also present a multi-organ involvement, including the biliary tree, joints and uvea. To detect a possible subclinical thyroid involvement, thyroid volume and function were assessed in 31 patients with IBD in active phase and in 50 control subjects. Thyroid volume was calculated by ultrasonography on the basis of the three maximum diameters of the 2 lobes. A blood sample was taken to determine free thyroid hormones, TSH, and anti-thyroid antibodies. In patients with IBD, thyroid volume was increased on average by 35%, and the prevalence of thyroid enlargements (antero-posterior diameter > 20 mm) was 3 times higher (45% vs 16%). Free thyroxine was increased by nearly 50%, but only 10% of patients had anti-thyroid antibodies. Alterations of thyroid volume and function are present in IBD, even in the absence of clinically-detectable thyroid disease. The association of IBD with thyroid disorders, as well as the involvement of various organs, confirms the view that IBD is a systemic disease.

Adult↗

[Diagnostic and prognostic significance of long latency reflexes, somatosensory evoked potentials and the blink reflex in cerebral ischemia].

In order to determine diagnostic and prognostic value of long latency reflexes, blink reflex and somatosensory evoked potentials in patients with ischemic brain disease (IBD), examinations were done in 32 patients of both sexes with IBD, average age 44-76 years. First examinations were performed within first week of the onset of IBD and in majority of patients repeated after 3 and 6 months. Changes of electrophysiological characteristics compared with the degree of IBD, clinical presentation, localization, extent of infarction zone (measured by CT) and functional recovery where analyzed. Electrophysiological changes were predominantly associated with amplitude of physiological response and were in correlation with the degree of IBD, localization and the extent of infarction zone. Latencies were prolonged only in case of subcortical ischemic lesions. Correlation between functional recovery and electrophysiological changes was present only within the structures responsible for certain components of electrophysiological responses and localization of ischemic lesion. In conclusion, electrophysiological examinations are of high diagnostic and predictive value in IBD.

Adult↗

Nonparametric simulation-based statistics for detecting linkage in general pedigrees.

We present here four nonparametric statistics for linkage analysis that test whether pairs of affected relatives share marker alleles more often than expected. These statistics are based on simulating the null distribution of a given statistic conditional on the unaffecteds' marker genotypes. Each statistic uses a different measure of marker sharing: the SimAPM statistic uses the simulation-based affected-pedigree-member measure based on identity-by-state (IBS) sharing. The SimKIN (kinship) measure is 1.0 for identity-by-descent (IBD) sharing, 0.0 for no IBD status sharing, and the kinship coefficient when the IBD status is ambiguous. The simulation-based IBD (SimIBD) statistic uses a recursive algorithm to determine the probability of two affecteds sharing a specific allele IBD. The SimISO statistic is identical to SimIBD, except that it also measures marker similarity between unaffected pairs. We evaluated our statistics on data simulated under different two-locus disease models, comparing our results to those obtained with several other nonparametric statistics. Use of IBD information produces dramatic increases in power over the SimAPM method, which uses only IBS information. The power of our best statistic in most cases meets or exceeds the power of the other nonparametric statistics. Furthermore, our statistics perform comparisons between all affected relative pairs within general pedigrees and are not restricted to sib pairs or nuclear families.

Algorithms↗

Incidence of inflammatory bowel disease in the province of Liège (Belgium). La Société de Gastroentérologie Liègeoise.

UNLABELLED: Up to now, as there is no national registry of patients with inflammatory bowel disease (IBD) in Belgium, the study of IBD epidemiology in our country is only possible through institutional or regional series. Therefore we conducted a prospective epidemiologic study of IBD in the Province of Liège (1 million inhabitants). METHODS: 29 (out of 47) private and public gastroenterologists completed a standard questionnaire for each patient consulting for the first time with clinical symptoms compatible with IBD between 1/06/1993 and 31/05/1994. RESULTS: During that period 104 cases of IBD were recorded: 56 (54%) Crohn's disease (CD), 36 (35%) ulcerative colitis (UC) including 7 proctitis (19% of UC) and 12 (11%) unclassified colitis. The annual incidence was 5.5 per 100.000 for CD and 3.5 for UC. The sex ratio F/M was 1.7 for CD and 0.7 for UC. The median age at the time of diagnosis was 33.5 yrs for CD and 40 yrs for UC. The highest age specific incidence rate for CD and UC was between 20 and 29 yrs : 13.6 and 6.1, respectively. CONCLUSIONS: This first Belgian prospective study has shown an incidence rate for CD comparable with that seen in north European studies but lower than that seen for UC. These results were similar to those observed in the northern part of France. Belgium appears to be a privileged country to undertake a national register and to study epidemiological aspects of IBD.

Adult↗

Morphometric evaluation of immunoglobulin A-containing and immunoglobulin G-containing cells and T cells in duodenal mucosa from healthy dogs and from dogs with inflammatory bowel disease or nonspecific gastroenteritis.

OBJECTIVE: To investigate the distribution of IgA- and IgG-containing cells and T cells in the villi of duodenal mucosa from healthy dogs and from dogs with inflammatory bowel disease (IBD) of gastroenteritis. DESIGN: Case-control study. ANIMALS: 28 dogs, grouped according to clinical and histologic criteria: 11 dogs with IBD, 8 dogs with non-specific gastroenteritis, and 9 healthy dogs. PROCEDURE: Endoscopic biopsy specimens of duodenal mucosa from each dog were stained specifically for IgA and IgG heavy chains and pan T-cell (CD3) antigen, using immunoperoxidase techniques. Morphometric analysis, performed via an image-analysis system, was used to count IgA- and IgG-containing cells and T cells within paired contiguous villi from each dog. RESULTS: cells were the predominant immune cell type in all groups of dogs. Significant differences in the villus distribution of IgA- and IgG-containing cells and T cells were not observed. Healthy dogs had significantly higher T-cell counts than had dogs with IBD or gastroenteritis. Dogs with nonspecific gastroenteritis had a significantly higher concentration of IgA-containing cells than the other groups of dogs had. Significant group differences for IgG-containing cells also were evident, with dogs with IBD having the lowest cell counts. CONCLUSIONS AND CLINICAL RELEVANCE: High concentrations of IgA- and IgG-containing cells and T cells in the villus lamina propria cannot be reliably used to distinguish IBD from other intestinal disorders in dogs. Evaluation of T cells may be the most discriminatory method for differentiating dogs with IBD from clinically normal dogs via examination of intestinal biopsy specimens.

Animals↗

[Enteropathic spondylarthritis in chronic inflammatory bowel diseases: prevalence, manifestation pattern and HLA association].

BACKGROUND: Enteropathic spondylarthropathies (SpA) are the most frequent extraintestinal manifestation of the chronic inflammatory bowel disease (IBD), Crohn's disease (CD) and Ulcerative Colitis (UC). It was the aim of the present study, to analyze a large number of IBD patients for the prevalence and pattern of joint manifestation and the association of SpA with the extend of bowel involvement and HLA-haplotype. PATIENTS AND METHODS: 521 patients (409 CD and 112 UC) were prospectively analyzed over a period of one year. SpA was diagnosed on the basis of an appropriate patient history as well as clinical, radiological and immunoserological parameters. RESULTS: SpA was diagnosed in 10.7% of all CD and 14.4% of all UC patients. In 26.8% of all patients symptoms of SpA occurred prior to and in 14.4% simultaneously with IBD. 28.1% of all patients presented with isolated peripheral arthritis, 26.8% of all patients showed an isolated involvement of the spine or sacroiliic joints and 45.1% of all patients presented with combined involvement. 2/12 UC patients with SpA suffered from rectosigmoiditis, 5/12 from partial colitis and 5/12 had pancolitis. In CD patients with SpA, 8/59 had isolated colitis, 8/59 ileocolitis and 31/59 isolated small bowel involvement. There was a positive correlation between SpA and HLA-B27 (p < 0.01). CONCLUSION: Enteropathic spondylarthropathies are an important extraintestinal manifestation of IBD. Spondylarthropathies occur irrespective of the extend of IBD and frequently become symptomatic prior to IBD. These and recent data describing inflammatory bowel disease in patients with SpA of unknown etiology suggest that both diseases have a common pathogenetic background.

Adult↗

The evolution of spondyloarthropathies in relation to gut histology. II. Histological aspects.

OBJECTIVE: To study prospectively the clinical evolution of different forms of spondyloarthropathy (SpA) in relation to the type of gut histology in ileocolonoscopic biopsy specimens. METHODS: Ileocolonoscopy was performed in 217 patients with SpA (149 men, 68 women). Three types of gut histology (normal gut histology and acute and chronic inflammatory gut lesions) were found. Clinical, laboratory, and radiological examinations were performed at start and 2 to 9 years later in 123 patients who were regularly monitored. For the remaining 94 patients clinical data were obtained by telephone. RESULTS: Of the 123 patients monitored regularly, 40 (32%) had normal gut histology, and 28 (23%) had acute and 55 (45%) chronic inflammatory gut lesions. Acute lesions were preferentially found in patients with non-ankylosing spondylitis SpA (non-AS-SpA). In the groups with normal gut histology and with chronic gut inflammation, patients with ankylosing spondylitis (AS) and non-AS-SpA were present in equal numbers. At review, clinical evolution was identical in the 3 histological subgroups. Eight patients developed idiopathic inflammatory bowel disease (IBD), one with initially acute gut inflammation, 7 with initially chronic gut inflammation. All had active AS at review. Fourteen patients with non-AS-SpA developed AS; 13 of them had initially presented inflammatory gut lesions. Three patients in the telephone group also developed IBD; all had active AS at review and initially presented chronic inflammatory gut lesions. Persistently high inflammatory serum variables, HLA-B27 negativity in the presence of sacroiliitis or AS, and inflammatory gut lesions at the first ileocolonoscopy indicate patients with SpA are at risk for developing IBD. CONCLUSION: Gut inflammation, mainly subclinical, could be demonstrated in 68% of patients with SpA. Acute gut inflammation was predominant in patients with reactive arthritis (ReA). The evolution to clinical remission was not influenced by the presence or the type of gut inflammation at start. Patients with non-AS-SpA with inflammatory gut lesions have greater risk of developing AS. One patient with Yersinia induced ReA developed AS and IBD. In total, 11 patients (66%) developed IBD, all initially presenting inflammatory gut lesions. Ten had chronic gut lesions, suggesting this type of gut inflammation is related to the inflammation of Crohn's disease. This type of gut inflammation, the persistence of high inflammatory serum variables, and the absence of HLA-B27 in patients with AS are risk factors for developing IBD.

Adolescent↗

Accelerated inflammatory bowel disease of TCR-alpha-deficient mice persistently infected with Cryptosporidium parvum.

TCR-alpha-deficient mice spontaneously develop inflammatory bowel disease (IBD) at 8-9 mo old. This study characterizes an accelerated form of IBD induced by Cryptosporidium parvum infection. Cryptosporidium parvum-infected TCR-alpha-deficient mice developed IBD as early as 4 wk old when challenged at 1 wk old. The lesions of this accelerated IBD resembled the lesions of spontaneous IBD in TCR-alpha-deficient mice and consisted of a mononuclear cell infiltrate within the intestinal lamina propria and an increased proliferation of enterocytes. The mononuclear cells within the lamina propria consisted of B cells and gamma delta T cells. The distal ileum, cecum, and colon were grossly thickened due to a hyperplastic mucosa and edematous submucosa. The mechanism by which C. parvum infection accelerates development of IBD is presently unclear.

Animals↗

Altered bone metabolism in inflammatory bowel disease.

UNLABELLED: A reduced bone mineral density has been reported in inflammatory bowel disease (IBD). OBJECTIVE: To assess the mechanisms of bone disease in IBD. METHODS: We studied in 90 patients (61 with Crohn's disease, 22 with ulcerative colitis, 7 with indeterminate colitis) biochemical markers of bone metabolism in serum and bone mineral density by peripheral quantitative computed tomography at the forearm. RESULTS: Forty-five percent of the patients had a reduced bone density (Z score < -1). Serum calcium was normal in most patients, vitamin D deficiency was documented in 17%. Osteocalcin, a serum marker of bone formation, was decreased in 26% (1.2 +/- 0.1 ng/ml), whereas the carboxyterminal cross-linked telopeptide of type I collagen (ICTP), a recently described serum parameter of bone breakdown, was stimulated in 38% (10.4 +/- 2.3 microg/L). Of 33 patients with increased ICTP levels, 19 showed a decreased bone density (Z score < -1), and 2 of them never received steroids. An active status of the underlying disease in most patients with increased ICTP levels suggests a direct effect of the underlying IBD. In the whole series of patients with a history of active disease (n = 34), 47% had signs of an increased bone degradation (ICTP > 5 microg/L; mean, 12.9 +/- 4.7 microg/L). Data derived from a retrospective survey of 245 patients with IBD suggest that the prevalence of bone fractures in IBD is unexpectedly high, particularly in patients with a long duration of disease, frequent active phases, and high cumulative doses of corticosteroid intake. CONCLUSIONS: Several mechanisms may be involved in IBD-associated bone disease: (1) a high inflammatory activity directly induces bone degradation via yet unknown pathways, (2) treatment with corticosteroids may exert catabolic effects on the bone, or (3) malabsorption and vitamin D deficiency may activate bone turnover.

Adolescent↗