Bone mineral status, bone turnover markers and vitamin D status in children with congenital adrenal hyperplasia

AIM: Treatment of congenital adrenal hyperplasia (CAH) consists of lifelong glucocorticoid therapy (GT), and long-term GT may cause osteoporosis. We aim to analyse bone mineral status (BMS) and bone turnover markers in children with CAH. Methods. The study included 17 patients with CAH (mean age ± SD; 7.96± 3.58 years, range 3-13.3 years) and age-matched controls. Bone metabolism rate, vitamin D status and BMS were analyzed. Alterations in bone metabolism rate were prospectively evaluated. Results. We found that BMS Z score did not differ between the patients and control group. Vitamin D deficiency is common in groups, and osteocalcin, β crosslaps and PTH was higher in patients than the healthy controls (5.3±3.4 vs. 3.2±1.8, P=0.036 and 2.19±1.59 vs. 1.27±0.99, P=0.049, 38.1±18.3 vs. 22.7±13.3, P=0.009, respectively). BMS Z score was only positively correlated with 17 OHP levels (r=0.462, P=0.05) and height SD Z scores (r=0.477, P=0.049). Seasonal measurements of vitamin D status, PTH levels and bone turnover markers exhibit that PTH levels, osteocalcin and β crosslaps increase in response to low vitamin D levels. Conclusion. Children with CAH have BMS values that are not different age-matched controls. Vitamin D status should be systematically measured in CAH patients, and supplementation should be recommended in patients with low vitamin D levels.     

Bone mineral density and bone turnover in patients with psoriatic arthritis

Psoriasis is a common inflammatory skin disease, and conflicting data have been published about osteoporosis and bone turnover markers in patients with psoriatic arthritis. The aim of this study was to assess bone mineral density (BMD) and bone turnover markers in psoriatic patients with and without peripheral arthritis and to investigate the relationship between clinical parameters and markers of bone turnover. Forty-seven patients (24 women, 23 men) with psoriasis were included to the study. Demographic data and clinical characteristics were recorded. Erythrocyte sedimentation rate and C-reactive protein were assessed as disease activity parameters. BMD was determined for lumbar spine and total hip by dual X-ray absorptiometry (DXA). Serum Ca, P, alkalen phosphatase (ALP), and serum type I collagen cross-linked C telopeptide (CTX) were measured as bone turnover markers in all patients. The patients were divided into two groups according to their peripheral arthritis status. The clinical and laboratory variables, as well as bone mass status of the groups, were compared with each other. Eighteen patients had peripheral arthritis. All the female patients were premenopausal. None of the patients had radiologically assessed axial involvement. There was no significant difference between the BMD levels of psoriatic patients with and without arthropathy. One patient (5%) had osteoporosis, and nine (50%) patients had osteopenia in arthritic group, while eight (27.5%) patients had osteopenia in patients without arthritis. Serum CTX, ALP, Ca, and P levels were not significantly different in arthritic than in non-arthritic patients (p > 0.05). In patients with psoriatic arthritis, the duration of arthritis was negatively correlated with BMD values of lumbar spine and total femur and serum CTX levels, suggesting an association of increased demineralization with the duration of joint disease. In conclusion, psoriatic patients with peripheral arthritis with longer duration of joint disease may be at a risk for osteoporosis, which can require preventative treatment efforts.     

Long-term corticosteroid replacement and bone mineral density in adult women with classical congenital adrenal hyperplasia

CONTEXT: Concern has been raised regarding the potential impact of chronic glucocorticoid therapy on the bone mineral density (BMD) of patients with congenital adrenal hyperplasia (CAH). OBJECTIVE: The purpose of this investigation was to assess the impact of chronic glucocorticoid replacement in adult women with classical CAH. PATIENTS AND DESIGN: We used dual energy x-ray absorptiometry to evaluate lumbar spine and whole body BMD in 11 women with salt-losing (SL) CAH and 15 with the simple virilizing form. Physical characteristics and serum hormone concentrations were also measured. Results were compared with those of unaffected sisters of CAH patients (n = 9). MAIN OUTCOME MEASURE: BMD was the main outcome measure. RESULTS: Osteopenia was noted in 45% of SL CAH patients, 13% of patients with the simple virilizing form, and 11% of controls. Lumbar spine and whole body BMDs of CAH subjects were lower than those of controls (P < 0.05). Compared with CAH subjects with normal BMD, those with osteopenia had reduced serum levels of dehydroepiandrosterone sulfate and dehydroepiandrosterone. Adrenal androgen levels were particularly suppressed among postmenopausal women receiving glucocorticoid replacement. CONCLUSIONS: Adult women with classical CAH treated with long-term glucocorticoids are at risk for decreased BMD, especially those with the SL form. Oversuppression of adrenal androgens is associated with increased risk for bone loss in this population.     

Bone turnover markers and bone mineral density in children with haemophilia

Summary. During childhood growth, bone undergoes modelling involving separate osteoblastic and osteoclastic processes. Markers of bone turnover circulate at high concentrations, parallel the childhood growth curve and correlate with height velocity. The aim of this study was to compare serum markers of bone turnover in children with haemophilia and normal bone mineral density (BMD) vs. those with low BMD. In a cross‐sectional study, 69 children with haemophilia were evaluated, 45 children with normal spine BMD vs. 24 with low BMD. Lumbar spine BMD was determined using dual X‐ray absorptiometry and Z‐scores were calculated. Serum samples of markers of bone turnover, osteocalcin (bone formation) and C‐telopeptide of type I collagen (bone resorption) were measured using ELISA. The mean BMD (g cm^?2) in the normal group was 0.656 ± 0.15 vs. 0.558 ± 0.12 in those with low BMD (P = 0.007), osteocalcin levels in children with normal BMD were 9.29 ± 4.97 vs. 7.06 ± 2.17 ng μL^?1 in the low BMD group (P = 0.012). C‐telopeptide levels in the normal group were 1.06 ± 1.4 vs. 0.74 ± 0.3 ng mL^?1 in the low BMD group (P = 0.169). Our results showed that low osteocalcin levels predominated in the group with low BMD, which indicates a diminished osteoblastic bone formation activity while there were no differences with regard to bone resorption markers. Moreover, osteocalcin levels explain 10% of the variation of lumbar spine Z‐score.     

Bone mineral density and bone turnover in spinal osteoarthrosis.

OBJECTIVES--To determine whether there was a generalised increase in bone mineral density (BMD) in spinal osteoarthrosis (OA), and to determine the mechanism of this possible protection against osteoporosis as assessed by biochemical markers of bone turnover. METHODS--We studied 375 women (ages 50 to 85) from a population based group. Spinal OA was defined from radiographs as the presence of degenerative changes affecting intervertebral or facet joints. BMD of the lumbar spine (LS), femoral neck (FN) and total body (TB) was measured by dual energy x ray absorptiometry (Lunar DPX). Bone turnover rates were estimated from measurement of biochemical markers of bone formation and resorption (urine deoxypyridinoline (Dpyr) and serum bone specific alkaline phosphatase (BAP)). RESULTS--BMD at each site was greater in the women with spinal OA (mean increase in LS-BMD 7.9%, 95% confidence interval (CI) 1.0 to 15.1; TB-BMD 8.4%, 95% CI 1.9 to 9.7; FN-BMD 6.4%, 95% CI 0.3 to 12.6). Twenty four hour urinary excretion of Dpyr, corrected for TB bone mineral content, and serum BAP were 19% lower in the women with spinal OA (95% CI for Dpyr 4.3 to 31.9%; for BAP 6.3 to 32.0%). CONCLUSIONS--Spinal OA is associated with a generalised increase in BMD and a decreased rate of bone turnover. This suggests that the protective effect of spinal OA against osteoporosis may be mediated by decreased bone turnover.     

Normal bone mineral density and lean body mass,but increased fat mass,in young adult patients with congenital adrenal hyperplasia

Patients with congenital adrenal hyperplasia attributable to 21-hydroxylase deficiency are treated with glucocorticoids. Glucocorticoid administration, even in substitution doses, may cause decreased bone mineral density (BMD) and obesity. The purpose of this study was to determine BMD, lean mass, and fat mass in young adult male (M, n = 15) and female (F, n = 15) patients with 21-hydroxylase deficiency, who had been treated with currently recommended low doses of glucocorticoids. Measurements were performed with dual-x-ray absorptiometry. In addition, calcaneal ultrasound measurements were performed (broadband ultrasound attenuation and speed of sound). Results were compared with those in age- and sex-matched controls; to adjust for height, lean and fat mass were divided by (height)(2). M and F patients [M, 21.7 +/- 2.4; F, 20.6 +/- 2.9 yr old (mean +/- SD)] were shorter than the controls (M, P < 0.001; F, P < 0.003) and their body mass indices were higher [M patients (25.0 +/- 3.6) vs. controls (22.3 +/- 1.9 kg/m(2)) (P < 0.02); F patients (25.5 +/- 4.5) vs. controls (21.9 +/- 2.3 kg/m(2)) (P < 0.02)]. BMD values (lumbar spine L1-L4, femoral neck, and total body) were not different from controls. Calcaneal ultrasound measurements showed that M patients had higher speed of sound values [M patients (1564 +/- 38) vs. controls (1529 +/- 29 m/sec) (P < 0.01)]. Lean mass in M and F patients was not different from controls when adjusted for height. Fat mass was higher in M and F patients when adjusted for height [M patients 5.6 +/- 2.9 vs. controls 2.7 median (1.7-7.0 min-max) kg/m(2) (P < 0.04); F patients 8.7 +/- 2.8 vs. controls 5.8 (4.3-10.7) kg/m(2) (P < 0.02)]. Relative fat mass (fat mass as a percentage of the total body mass) was higher in patients, compared with controls [M patients 22.0 +/- 9.1 vs. controls 12.8 (8.5-27.0)% (P < 0.04); F patients 34.1 +/- 5.0 vs. controls 29.0 +/- 5.1% (P < 0.02)]; this resulted from increased fat mass, not from decreased lean mass. Fat distribution over the body was not different in patients and controls. No significant correlations were found between cumulative glucocorticoid doses in the last 0.5, 2, or 5 yr or mean salivary morning levels of 17-hydroxyprogesterone and androstenedione in the last 5 yr on one hand and bone parameters, lean mass, or fat mass on the other hand. We conclude that, at prevailing low-dose glucocorticoid regimens, young adult patients with 21-hydroxylase deficiency have normal BMD. Their lean mass is in accordance with height, but fat mass is increased, with a normal distribution over the body. This results in a higher fat percentage of the total body and a higher body mass index than in healthy peers. Because overweight and increased fat mass are associated with the metabolic syndrome and increased cardiovascular risk, weight management should have appropriate attention in the follow-up of congenital adrenal hyperplasia patients, to prevent overweight-associated morbidity.     

Bone turnover markers predict changes in bone mineral density after parathyroidectomy in patients with renal hyperparathyroidism

Objective Patients on long‐term dialysis may develop secondary hyperparathyroidism (SHPT), which causes varying degrees of bone mass loss. This condition is treated with parathyroidectomy (PTX). We investigated whether serial serum bone turnover markers could predict changes in bone mineral density (BMD) after PTX. Design and patients Renal patients on maintenance haemodialysis who received PTX for refractory SHPT (n = 26, male/female: 13/13; mean age: 48·6 ± 10·7 year) and control subjects without SHPT (n = 25) were prospectively followed for 1 year at two tertiary hospitals in Taiwan. Measurements Serum intact parathyroid hormone (iPTH), bone‐specific alkaline phosphatase (BAP) and type 5b tartrate‐resistant acid phosphatase (TRAP) were measured serially. Additionally, femoral neck (FN) and lumbar spine (LS) BMD were measured before and 1 year after PTX. Results After PTX, iPTH levels decreased markedly and persistently. BMDs increased in both the FN and LS, but particularly in the LS. Serum BAP progressively increased to a peak at 2 weeks after PTX. Serum TRAP levels progressively decreased over 6 months after PTX. In univariate correlation analyses, baseline iPTH correlated positively with T‐score changes in FN (r = 0·45, P = 0·021) and LS (r = 0·48, P = 0·013). In multivariate regression models, changes in FN T‐scores were negatively predicted by baseline BAP levels (r = ?0·615, P = 0·005) and baseline FN T‐scores (r = ?0·563, P = 0·012), and they were positively predicted by baseline TRAP(r = 0·6, P = 0·007). Changes in LS T‐scores were positively predicted by baseline TRAP values (r = 0·528, P = 0·01) and negatively predicted by the percentage change in BAP after 2 weeks (r = ?0·501, P = 0·015). Conclusions Parathyroidectomy provided marked, sustained improvements in BMD for up to 1 year. Furthermore, markers of bone turnover predicted 1‐year changes in FN and LS BMDs after PTX.     

Bone density and bone turnover in patients with osteoarthritis and osteoporosis

OBJECTIVE: Osteoarthritis (OA) and osteoporosis (OP) are reported to be rare in the same patient. We examined bone mass, bone turnover, and radiological presence of OA in a group of patients with OA with previous hip fractures and age matched controls. METHODS: Bone mass was assessed by bone mineral density (BMD), using dual energy x-ray absorptiometry (DEXA) of the hip and total body, and quantitative ultrasound of the os calcis, measuring broadband ultrasound attenuation and velocity of sound. Bone turnover was assessed by measuring urinary pyridinium crosslinks and serum osteocalcin. RESULTS: There were differences in bone density, the patients with OP having lower bone density, while patients with OA had similar or increased bone density compared to controls, Serum osteocalcin showed no significant differences among the 3 groups of patients. Urinary pyridinium crosslinks excretion was significantly elevated in the OA group but not in the OP group compared with controls. CONCLUSION: Increased bone turnover was restricted to the OA group.     

胰岛素、胰岛素原对胰岛素抵抗状态下HepG2细胞PAI-1分泌的影响

目的研究胰岛素、胰岛素原对胰岛素抵抗状态下ＨｅｐＧ２细胞ＰＡＩ１分泌的影响。方法选择在合成ＰＡＩ１方面与肝细胞相似的ＨｅｐＧ２细胞，以高浓度胰岛素诱导胰岛素抵抗后，分别用生理浓度的胰岛素、胰岛素原刺激２４小时，以观察胰岛素抵抗状态下ＰＡＩ１活性的变化。结果基础状态下胰岛素抵抗ＨｅｐＧ２细胞与非胰岛素抵抗ＨｅｐＧ２细胞相比，ＰＡＩ１活性差异不明显；胰岛素、胰岛素原刺激后，胰岛素抵抗ＨｅｐＧ２细胞ＰＡＩ１活性明显高于非胰岛素抵抗ＨｅｐＧ２细胞。当培液中同时加入１０－４Ｍ二甲双胍后，胰岛素、胰岛素原介导的ＰＡＩ１过量分泌得到明显抑制。结论在胰岛素抵抗状态下，胰岛素、胰岛素原刺激后ＨｅｐＧ２细胞ＰＡＩ１活性明显增加，而二甲双胍可明显抑制此现象。     

Bone mineral density, calcaneal ultrasound, and bone turnover markers in women with ankylosing spondylitis

OBJECTIVE: To assess bone mineral density (BMD) by dual energy x-ray absorptiometry (DEXA) and calcaneal quantitative ultrasound (QUS) in a cohort of pre- and postmenopausal women with ankylosing spondylitis (AS), and to determine any relationships with markers of bone turnover and disease activity or severity. METHODS: Fifty premenopausal and 16 postmenopausal women with AS were studied. Clinical and radiological status was assessed by the Bath AS Disease Activity Index (BASDAI), Bath AS Functional Index (BASFI), Bath AS Metrology Index (BASMI), and Bath AS Radiology Index (BASRI). BMD of the hip and spine was measured by DEXA, and QUS measured at the heel. Serum osteocalcin (OC), bone-specific alkaline phosphatase (BALP), urinary D-pyridinoline crosslinks (D-PYR), and C-reactive protein (CRP) were assayed. RESULTS: Women with AS (n = 66) had reduced BMD at the hip compared to age and sex matched controls (n = 132). The mean t scores were -1.1 and -2.0, and z scores -0.4 and -0.37, for pre- and postmenopausal women, respectively. Four (6%) had osteoporosis and 34 (52%) had osteopenia according to the WHO definitions. Using a multiple regression model, femoral neck BMD was found to be significantly affected by age, body mass index, and the sacroiliac radiographic score. There were no significant correlations of BMD with disease duration or disease activity. QUS measures did not correlate with DEXA measures of BMD. Women with AS had significantly lower markers of bone formation, OC and BALP, and a trend to higher D-PYR than controls. Serum OC levels correlated negatively with femoral neck BMD, whereas D-PYR correlated with CRP levels. CONCLUSION: Women with AS have reduced hip BMD, 0.39 SD below age and sex matched controls. Bone turnover in women with AS is characterized by low OC and BALP.     

Bone mineral density and biological markers of bone repair in patients with adrenal incidentaloma: effect of subclinical hypercortisolism

PURPOSE: Some adrenal incidentalomas produce cortisol in mild excess ('subclinical' Cushing's adenomas) and can potentially induce osteopenia. Their diagnosis is usually based on exclusive tumour uptake on adrenal scintigraphy using 131I-6 beta-methyl-iodo-19-norcholesterol and on inadequate cortisol response to dexamethasone (DXM) suppression tests. The aims of the present study were to evaluate bone mineral density (BMD) and metabolic markers of bone turnover in patients with incidentalomas and to test the effect of mild hypercortisolism on bone parameters. METHODS: Thirty-five patients (13 men, 22 postmenopausal women, 49-76 years) with unilateral incidentaloma were studied. BMD was measured by dual X-ray absorptiometry. Two biochemical markers of bone formation, serum osteocalcin (BGP) and bone alkaline phosphatase (bALP), and two markers of bone resorption, urinary free deoxypyridinoline (D-Pyr) and urinary carboxy-telopeptide of bone type 1 collagen (CTX), were measured by radioimmunoassay. D-Pyr and CTX were corrected for creatinine excretion. RESULTS: Median values of lumbar and femoral T-score were -1.125 and -0.920, respectively, whereas corresponding Z-score values where normal (0.105 and 0.120, respectively). Thirty-nine percent of patients had low serum BGP values and 3% had low bALP values; 16% showed elevated D-Pyr/creatinine values and 23% increased CTX/creatinine values. Patients both with suppression of the contralateral adrenal on scintigraphy and with an inadequate cortisol response to 1 mg DXM (> 50 nmol/L) (n = 14) presented a lower femoral T-score (P < 0.02) and, to a lesser extent, a lower femoral Z-score (P = 0.11) than other patients (n = 21). The proportion of increased values of CTX/creatinine (42% versus 11%, P = 0.08) also tended to be higher in the first than in the second group of patients. These two groups of patients were similar in terms of age, but tumour size was larger (P < 0.04) and plasma ACTH value was lower (P < 0.02) in patients with scintigraphic and endocrine abnormalities. CONCLUSION: Subclinical hypercortisolism defined on the basis of scintigraphic and hormonal criteria seems to contribute to bone loss in patients with adrenal incidentaloma. As other possible side effects of mild hypercortisolism, these findings have to be taken into account in the therapeutic management of these patients.     

Bone mineral density in patients with rheumatoid arthritis: relation between disease severity and low bone mineral density

OBJECTIVE: To examine variables associated with bone mineral density (BMD) in patients with rheumatoid arthritis (RA). METHODS: We investigated 373 patients with low to moderately active RA. Patients with low disease activity were recruited from a cohort of patients in clinical remission. Patients with moderately active disease were included in a trial comparing the effects of long term high intensity exercise programme and conventional physical therapy. Demographic and clinical data were collected. Bone mineral density (BMD) was measured by means of dual x ray absorptiometry (DXA). Associations between demographic and clinical measurements on the one hand and BMD on the other were investigated in regression analyses. RESULTS: The patient group consisted of middle aged, mainly female, patients. The median (interquartile range) disease duration was 7 (4 to 13) years, the mean disease activity score (standard deviation) was 3.2 (1.4). Of the group, 66% was rheumatoid factor positive, and 83% (n = 304) had never used corticosteroids. The median Larsen score of hands and feet was 27 (5 to 61). Greater age and low body mass index were related to low BMD at the hip and spine. High Larsen score for hands and feet was significantly associated with low BMD at the hip. The use of corticosteroids was not independently associated with BMD. The results of the multiple regression analyses also applied to the subgroup of corticosteroid naive patients. CONCLUSION: BMD data of patients with low to moderately active RA demonstrated an association between high radiological RA damage and low BMD at the hip, which suggests an association between the severity of RA and the risk of generalised bone loss, which also occurred in corticosteroid naive patients.     

Bone mineral density and markers of bone turnover in boys with constitutional delay of growth and puberty

It has been suggested that poor growth in childhood or puberty might be a correctable determinant of osteoporosis. To assess the effect of the growth and puberty delay on bone metabolism, we measured bone mineral density (BMD) and markers of bone turnover in 41 boys with constitutional delay of growth and puberty. Total body (TB) and lumbar spine (LS) BMD were measured by dual-energy x-ray absorptiometry. Serum osteocalcin, total alkaline phosphatase, and urinary deoxypyridinoline cross-links as markers of bone turnover were evaluated. BMD was decreased by at least 1 sd in TB in 23 boys (56%) and in LS in 27 boys (66%). After adjustment of BMD for bone age, TB was decreased in 11 boys (27%) and LS in 13 boys (32%). Bone age and chronological age significantly correlated with areal and volumetric BMD. The significant increments of height, weight, TB, and LS BMD between the consecutive pubertal stages were reported. Mean alkaline phosphatase, osteocalcin, and deoxypyridinoline were within reference ranges and showed no differences between pubertal stages. In conclusion, in boys with constitutional delay of growth and puberty, bone turnover is normal, and BMD increases in a manner similar to healthy children.     

Circadian hydrocortisone infusions in patients with adrenal insufficiency and congenital adrenal hyperplasia

OBJECTIVE: Conventional hydrocortisone therapy in adrenal insufficiency cannot provide physiological replacement. We have explored the potential of circadian delivery of hydrocortisone as proof of concept for such therapy delivered in modified-release tablet formulation. METHODS: We investigated whether the circadian intravenous infusion of hydrocortisone could improve control of ACTH and androgen levels. Two healthy subjects, two patients with Addison's disease and two patients with congenital adrenal hyperplasia (CAH) were studied. RESULTS: In patients on thrice daily oral hydrocortisone, peak serum cortisol levels were higher than in normal subjects and overnight levels were very low. Patients had very high plasma ACTH levels before their morning dose of hydrocortisone, both at the beginning and at the end of their conventional oral therapy: mean +/- SEM 311.8 +/- 123.2 and 311.2 +/- 85.4 ng/l, respectively. In the patients with CAH, serum 17-hydroxyprogesterone levels were also elevated: 550 and 642 nmol/l at the beginning and 550 and 777 nmol/l at the end of conventional treatment, respectively. The overall 24-h mean cortisol levels were similar for conventional oral hydrocortisone and the circadian infusion. At 0700 h, ACTH levels were much higher on conventional treatment than after circadian infusion: mean +/- SEM 311.2 +/- 85.4 vs. 70.5 +/- 45.0 ng/l, respectively (P < 0.05). The same pattern was observed in 17-hydroxyprogesterone levels, which were 550 and 777 nmol/l after conventional treatment and 3 and 64 nmol/l after circadian infusion. CONCLUSIONS: In patients with poor biochemical control of Addison's disease and CAH, a 24-h circadian infusion of hydrocortisone can decrease morning ACTH and 17-hydroxyprogesterone levels to near normal.