Bone-specific Alkaline Phosphate Research Articles

Roles of Follicle-Stimulating Hormone on Bone Metabolism in Late Postmenopausal Women.

BackgroundThe effects of elevated follicle-stimulating hormone (FSH) levels on physiological changes in the bone remain unclear. This study aimed to clarify the association between FSH concentrations and bone mineral density (BMD) and bone turnover markers (BTM) in late postmenopausal women.MethodsA total of 169 Korean women were enrolled. The participants’ ages ranged from 60 to 84 years (mean age, 69.0±5.1) and reported a mean duration of 19.4±6.6 years since menopause (YSM). The participants showed an average body mass index (BMI) of 24.4±2.8 kg/m2. Age, YSM, estradiol, testosterone, and BMI were confounders in the Pearson’s partial correlation. A test for trends across the quartiles of FSH levels was performed for each variable.ResultsThe mean FSH and estradiol concentrations were 61.5 IU/L and 2.9 pg/mL, respectively. Serum FSH concentration was not significantly associated with BMD (lumbar, r=0.09, P=0.30; total hip, r=0.00, P=0.96; and femoral neck, r=0.05, P=0.62). BTM across the FSH quartiles did not show any trend association (bone-specific alkaline phosphate, P=0.31; cross-linked C-terminal telopeptide of type I collagen, P=0.90). Instead, FSH levels were negatively correlated with BMI (r=−0.34, P=0.00). In the multivariate regression model adjusted for age, testosterone, and estradiol, only BMI showed a negative value across the FSH quartiles (β coefficient −0.11, P=0.00).ConclusionsThis study identified that high FSH concentrations were not associated with bone loss or high bone turnover in women in the late postmenopausal period.

Role of textural heterogeneity parameters in patient selection for 177Lu-PSMA therapy via response prediction.

PurposeProstate cancer is most common tumor in men causing significant patient mortality and morbidity. In newer diagnostic/therapeutic agents PSMA linked ones are specifically important. Analysis of textural heterogeneity parameters is associated with determination of innately aggressive and therapy resistant cell lines thus emphasizing their importance in therapy planning. The objective of current study was to assess predictive ability of tumor textural heterogeneity parameters from baseline 68Ga-PSMA PET prior to 177Lu-PSMA therapy.ResultsEntropy showed a negative correlation (rs = −0.327, p = 0.006, AUC = 0.695) and homogeneity showed a positive correlation (rs = 0.315, p = 0.008, AUC = 0.683) with change in pre and post therapy PSA levels.ConclusionsStudy showed potential for response prediction through baseline PET scan using textural features. It suggested that increase in heterogeneity of PSMA expression seems to be associated with an increased response to PSMA radionuclide therapy.Materials and MethodsRetrospective analysis of 70 patients was performed. All patients had metastatic prostate cancer and were planned to undergo 177Lu-PSMA therapy. Pre-therapeutic 68Ga- PSMA PET scans were used for analysis. 3D volumes (VOIs) of 3 lesions each in bones and lymph nodes were manually delineated in static PET images. Five PET based textural heterogeneity parameters (COV, entropy, homogeneity, contrast, size variation) were determined. Results obtained were then compared with clinical parameters including pre and post therapy PSA, alkaline phosphate, bone specific alkaline phosphate levels and ECOG criteria. Spearman correlation was used to determine statistical dependence among variables. ROC analysis was performed to estimate the optimal cutoff value and AUC.

Effects of Curcumin on Bone Loss and Biochemical Markers of Bone Turnover in Patients with Spinal Cord Injury.

Osteoporosis is one of the most common problems of patients with spinal cord injuries (SCIs). The current study aimed to evaluate the antiosteoporotic effects of curcumin on densitometry parameters and biomarkers of bone turnovers among patients with SCI. The current controlled clinical trial was conducted among 100 patients with SCI referred to an outpatient clinic of rehabilitation in Ilam City, Iran, in 2013-2015. The intervention group received 110/mg/kg/day curcumin for 6 months and the control group received placebo. Bone mineral density (BMD) was measured in all patients. The level of procollagen type I N-terminal propeptide, serum carboxy-terminal telopeptide of type I collagen, osteocalcin, and bone-specific alkaline phosphates were compared before and after study. BMD indicators of lumbar, femoral neck, and total hip in the control group significantly decreased compared with the beginning of study. However, in the curcumin group, a significant increase was observed in BMD indicators of lumbar, femoral neck, and hip at the end of study compared with the beginning. There was also a significant difference between interventional and control groups for the mean BMD of femoral neck and hip at the end of study (0.718 ± 0.002 g/cm2 vs. 0.712 ± 0.003 g/cm2 and 0.742 ± 0.031 g/cm2 vs. 0.692 ± 0.016 g/cm2, respectively). Curcumin, via modulation of densitometry indices and bone resorption markers, showed inhibitory effects on the process of osteoporosis. Treatment with curcumin was significantly associated with a decrease in the osteoporosis progression and bone turnover markers of patients with SCI after 6 months.

A retrospective analysis of bone mineral status in patients requiring spinal surgery

BackgroundImpaired bone quality is associated with poor outcome of spinal surgery. The aim of the study was to assess the bone mineral status of patients scheduled to undergo spinal surgery and to report frequencies of bone mineral disorders.MethodsWe retrospectively analyzed the bone mineral status of 144 patients requiring spinal surgery including bone mineral density by dual-energy X-ray absorptiometry (DXA) as well as laboratory data with serum levels of 25-hydroxyvitamin D (25-OH-D), parathyroid hormone, calcium, bone specific alkaline phosphate, osteocalcin, and gastrin. High-resolution peripheral quantitative computed tomography (HR-pQCT) was additionally performed in a subgroup of 67 patients with T-Score below − 1.5 or history of vertebral fracture.ResultsAmong 144 patients, 126 patients (87.5%) were older than 60 years. Mean age was 70.1 years. 42 patients (29.1%) had suffered from a vertebral compression fracture. 12 previously undiagnosed vertebral deformities were detected in 12 patients by vertebral fracture assessment (VFA). Osteoporosis was present in 39 patients (27.1%) and osteopenia in 63 patients (43.8%). Only 16 patients (11.1%) had received anti-osteoporotic therapy, while 54 patients (37.5%) had an indication for specific anti-osteoporotic therapy but had not received it yet. The majority of patients had inadequate vitamin D status (73.6%) and 34.7% of patients showed secondary hyperparathyroidism as a sign for a significant disturbed calcium homeostasis. In a subgroup of 67 patients, severe vertebral deformities were associated with stronger deficits in bone microarchitecture at the distal radius compared to the distal tibia.ConclusionsThis study shows that bone metabolism disorders are highly prevalent in elderly patients scheduled for spinal surgery. Vertebral deformities are associated with a predominant deterioration of bone microstructure at the distal radius. As impaired bone quality can compromise surgical outcome, we strongly recommend an evaluation of bone mineral status prior to operation and anti-osteoporotic therapy if necessary.

Vitamin D deficiency, bone turnover markers and causative factors among adolescents: a cross-sectional study

BackgroundThis cross-sectional population-based study was conducted to elucidate the prevalence of vitamin D deficiency, bone turnover marker’s variation and its influencing factors among adolescents of Tehran.MethodsTotally 444 middle and high school (53.6 % in high school) students (both girls and boys) were recruited. A short food frequency questionnaire designed to estimate dietary calcium and vitamin D consumption. Serum levels of calcium, phosphorus, parathyroid hormone (PTH), bone specific alkaline phosphates, 25 (OH) vitamin D, osteocalcin, cross-linked C-telopeptide (CTX), total protein, albumin and creatinine were determined.ResultsVitamin D deficiency was prevalent in adolescents and only 22.4 % of students had normal serum vitamin D. Results revealed that vitamin D insufficiency reported in 34.2 % of students and vitamin D deficiency was in 43.3 % of them. Serum vitamin D, osteocalcin, CTX and bone specific alkaline phosphates were significantly higher in boys in all different ages. Serum levels of 25 (OH) vitamin D had positive influences on bone turnover markers and had negative correlation with PTH.ConclusionsVitamin D deficiency and insufficiency is common among healthy adolescents of Tehran. There is a pressing need to improve vitamin D status among adolescents. Increasing vitamin D fortification of dairy products can be considered as a population-wide public health strategy in Iran.

Giant cell rich osteosarcoma revisited-diagnostic criteria and histopathologic patterns, Ki67, CDK4, and MDM2 expression, changes in response to bisphosphonate and denosumab treatment.

Defining giant cell-rich osteosarcoma (GCRO) as "an osteosarcoma in which more than 50% of the tumor consists of numerous uniformly distributed osteoclastic giant cells amidst oval or spindle mononuclear cells embedded in a fibrovascular stroma," eight such cases identified among 265 cases of osteosarcoma were analysed. Their age ranges from 11 to 33years, with peak incidence in the second decade and equal sex distribution. Seventy-five percent presented with pain, commonest in the knee, affecting the metaphysis. Most appeared radiologically as well-circumscribed expansile multiloculated osteolytic lesions, and many are displayed periosteal reaction. They showed several distinct histologic patterns: the stromal and giant cell, fibrohistiocytic, aneurysmal-cystic, osteoblastoma-like, and parosteal and fibrous dysplasia-like patterns. Focal subtle lacelike osteoid deposition, permeative infiltration into adjacent native bony trabeculae and over 30% Ki67 proliferative index were characteristic. There was no CDK4 and MDM2 amplification. In those having bisphosphonate and denosumab treatment, there was limited focal necrosis with reduction in the number of giant cells and broad trabecular woven bone formation but no giant osteoclast was seen. Two patients with initial diagnosis of giant cell tumor treated by curettage and local resection pursued aggressive clinical courses, died after 14 and 21months. The others survived 12 to 110months. GCRO accounts for about 3% of all osteosarcomas and apart from its more frequent diaphyseal location and associated normal bone-specific alkaline phosphate levels; it shares with conventional high-grade osteosarcoma the same patient demographics, sites of occurrence, absence of CDK4 and MDM2 amplification, and probably clinical course.

Sex hormone-binding globulin (SHBG) as an independent determinant of bone mineral density (BMD) among Chinese middle-aged and elderly men

The aim of the study was to assess the impact of sex hormone-binding globulin (SHBG) on bone mineral density (BMD) and bone turnover among Chinese middle-aged and elderly men. This cross-sectional study was carried out among 404 Chinese men aged over 45 years. BMD was measured with dual-energy X-ray absorptiometry, and participants' blood was collected for bone-specific alkaline phosphates (BSAP), SHBG and testosterone assay. Osteoporotic men had lower free testosterone (FT) and higher levels of SHBG, and BSAP than the osteopenia and normal groups. When SHBG levels were divided into quartiles, FT levels decreased and prevalence of osteoporosis increased with higher SHBG levels. Compared with subjects in the lowest quartile of SHBG levels (<36.55 nmol/l), subjects in the third quartile [OR (95 % CI) 2.998 (1.460-6.157), p = 0.002] and the highest quartile [OR (95 % CI) 4.439 (2.192-8.991), p < 0.001] were more likely to suffer with osteoporosis. FT was significantly positive related to total hip BMD and total lumbar BMD, whereas there was no association between TT and BMD after adjusting for age, BMI and FT. SHBG levels were also inversely related to BMD. SHBG could explain 1.4-2.1 % of the BMD variance after adjustment for age, BMI and FT. No association was found between BSAP and SHBG, TT and FT. Logistic regression analysis showed that BMI, smoking and FT or SHBG was independently associated with the presence of osteoporosis. Serum FT levels were positively correlated with BMD, while SHBG levels were inversely related to BMD. Increasing SHBG level was an independent risk factor for osteoporosis among Chinese men.

Age‐Related Serum Alkaline Phosphatase Trends

Biochemical markers of bone turnover have been shown to be useful as inexpensive and noninvasive tools for monitoring skeletal health. Because duel energy absorptiometry and other indicators of bone mineral density reflect changes to bone accumulated over months, we sought to assess bone health and to explore potential sex differences in bone metabolism. Bone‐specific alkaline phosphatase (ALP), 25‐hydroxy‐and 1, 25‐dihydroxyvitamin D, calcium, phosphate, and parathyroid hormone (PTH) in 359 men and women (n=77 and 282, respectively) between the ages of 18 and 80 years old. Subjects were placed in one of three age groups (20–50, 51–70 and &gt;;71 years of age for men and 18–40, 41–60, and &gt;;60 years of age for women, and into a self‐identified ethnicity category. As expected, we found a downward trend in bone densities as subjects got older. We also found that ALP values were significantly lower in the older cohort of males and significantly higher in the older cohort of females when compared to their respective younger cohort (p&lt;0.01). We propose an index utilizing PTH and ALP ratios that may reflect the metabolic direction for bone health. Given the complexities of hormonal, nutrient and activity levels of elderly subjects, these data suggest that the mechanisms that contribute to bone remodeling may be different in males when compared to females. This research was funded by Irvine Health Foundation.

Correlation of the levels of the bone turnover markers BAP and β-CTX with bone metastasis progress in lung cancer patients

背景与目的肺癌易发生骨转移，Ⅰ型胶原羧基端肽β特殊序列（β isomer of C-terminal telopeptide of type Ⅰ collagen, β-CTX）和骨源性碱性磷酸酶（bone-specific alkaline phosphates, BAP）在骨质代谢中是重要的生化标记物，本研究旨在探讨骨代谢生化指标和肺癌骨转移进展程度的相关性，有助于早期判断是否有肺癌骨转移的发生。方法天津市人民医院2009年7月-2012年7月共收治92例肺癌并发生骨转移患者，全部病例其原发灶均经细胞学检查证实，骨转移灶的数目及类型经ECT结合X线片、CT证实，采用ELISA方法检测血β-CTX、BAP的浓度水平。结果收集的92例肺癌伴骨转移的患者中，转移灶 < 3处为58例，≥3处为34例；溶骨型68例，成骨型9例，混合型15例。血β-CTX、BAP水平在不同的骨转移数目组间差异有统计学意义（P < 0.05），β-CTX在肺癌溶骨型骨转移患者中具有较高的敏感性。结论骨代谢生化指标β-CTX、BAP对肺癌骨转移具有辅助诊断意义，是判断转移进展程度的良好指标。

Long-term outcomes of children and adolescents who had cerebral palsy with secondary osteoporosis

Objective:To investigate the long-term efficacy and index of treatment with vitamin D alone or with a bisphosphonate in children and adolescents who have cerebral palsy (CP) with secondary osteoporosis.Research design and methods:Thirty patients diagnosed with CP and secondary osteoporosis were analyzed for 5 years, and the efficacy of treatment was compared. Treatment was divided into three groups: The monotherapy group, consisting of patients taking only alfacalcidol (0.03 µg/kg/day); the polytherapy group, consisting of those taking alfacalcidol and risedronate (0.05 mg/kg/day); and the control group, consisting of patients who discontinued taking their medications for reasons unrelated to these therapies. Bone mineral density (BMD), bone-specific alkaline phosphate (BAP), and N-telopeptides of type I collagen (NTX/Cr) were measured on each patient just before and at discontinuation of treatment, after 6 months, and again at 1 and 3 years, respectively. The changes in BMD (ΔBMD), BAP (ΔBAP), and NTX/Cr (ΔNTX/Cr) were evaluated at these intervals, because the normal value of each parameter varies over time during childhood.Results:ΔBMD significantly increased in the polytherapy group at ≥1 year (p = 0.006), and the difference in BMD between the polytherapy and the control groups at ≥1 year was also significant (p = 0.005). ΔBAP was increased in the monotherapy and polytherapy groups at ≥1 year (p = 0.021 and p = 0.033). ΔNTX/Cr decreased in the polytherapy group at ≥1 year, which was consistent with the polytherapy group of the period from 1 month to 1 year (p = 0.033). The relation between ΔBMD to ΔBAP was a positive correlation in the second period in the monotherapy group (r = 0.46). And the relations between ΔBMD to ΔNTX/Cr were not recognized negative correlations in the monotherapy and polytherapy groups. Thus, ΔBMD reflected ossification of secondary osteoporosis in patients with CP, and ΔBAP and ΔNTX/Cr was significantly related to the increase and decrease of ΔBMD. There were no effects of other factors except sexual maturity. Limitations of this study include that each index of examination was the evaluation according to rate of change. Therefore, the results of this study were limited to longitudinal evaluations.Conclusion:Evaluation according to ΔBMD and both methods of monotherapy and polytherapy were useful for CP patient taking antiepileptic drugs (AEDs) and regardless of sex. Especially, polytherapy for longer than 1 year led to improvement in BMD in children who had CP with secondary osteoporosis. BAP and NTX/Cr were useful for the index of the progression osteoporosis with or without these therapies.

Differences in bone metabolism between singleton pregnancy and twin pregnancy

The objective of this study was to examine the influence of twin pregnancy on calcium metabolism, including bone turnover markers and calcium-regulating factors, by comparison between singleton pregnancy and twin pregnancy in women during pregnancy and puerperium in cross-sectional and longitudinal studies. Women with singleton and twin pregnancies were recruited from the outpatient clinic of Tokushima University Hospital. In both cross-sectional and longitudinal studies, bone formation and resorption markers, mineral metabolism and calcium-regulating factors were measured at 10, 25, 30 and 36 weeks of pregnancy and at 4 days and 1 month postpartum in women with singleton and twin pregnancies. Urinary levels of cross-linked type I collagen N-telopeptides and C-terminal telopeptides of type I collagen in women with twin pregnancy were significantly higher than those in women with singleton pregnancy and those high levels were observed earlier than those in women with singleton pregnancy. In the cross-sectional study, serum levels of bone-specific alkaline phosphatase, calcium and phosphate in women with twin pregnancy were higher and the levels of 1,25-(OH)2 vitamin D and 25-(OH) vitamin D in women with twin pregnancy were lower than those in women with singleton pregnancy. Changes in bone metabolism in women with twin pregnancy are different from those in women with singleton pregnancy. Early and large increases in bone turnover markers allow women with twin pregnancy to meet high fetal demand for calcium during pregnancy.

Statins and bone health in postmenopausal women: a systematic review of randomized controlled trials

Basic science data, animal studies, and observational human studies suggest that the lipid-lowering cardiovascular family of statin medications might decrease fractures, increase bone density, and have a positive effect on bone turnover markers. The primary purpose of our review was to determine whether statins can prevent fractures in postmenopausal women; as secondary and explanatory factors, bone density and bone biomarker data were also evaluated. All randomized controlled trials assessing the effect of statins on bone mineral density were included; bone turnover markers and fractures in postmenopausal women were considered. We identified six randomized trials involving 3,022 participants. Statins had no association with decreasing incidence of fracture. There was no statistical difference in the reduction in lumbar spine or total hip bone density. Other predictors of osteoporosis-related fracture risk, including markers relating to bone resorption (c-telopeptide of type I collagen and n-telopeptide of type I collagen) and bone formation (osteocalcin and bone-specific alkaline phosphates), did not show any significant changes. The trials included in our review, which included data on 3,022 women (mean age, >62.7 y), do not indicate that statin use prevents fractures or increases bone density.

Osteogenic Index and Changes in Bone Markers during a Jump Training Program

This study was designed as a proof-of-concept study to assess the osteogenic index (OI) and changes in bone markers during an 8-wk jump training program. On the basis of the OI, jumps were completed in one or two daily sessions with total jumps per day being equal. Seven males served as controls and participated in their normal strength training program. Fourteen males were divided into two groups, jumping once daily (J1x) or jumping twice daily (J2x), with a 6-h recovery period between sessions (J2x only). Jumping-type exercises were performed on a Plyo Press and started at 20 plyo-jumps per day, three times per week and progressed to 60 plyo-jumps per day, three times per week for the last 3 wk. Blood samples were collected at baseline and at 4 and 8 wk to determine serum concentrations of bone-specific alkaline phosphate and C-terminal telopeptides of type I collagen. OI for each session and week were different (P < 0.05) between the two jumping groups (baseline OI per week, J1x = 28 +/- 0.9, J2x = 34 +/- 0.9). There was a significant change (P = 0.005) in bone-specific alkaline phosphate over time, with 8-wk values being significantly higher than baseline values (change from baseline: J1x = 2.7 +/- 1.4 microg.L-1, J2x = 3.5 +/- 1.3 microg.L-1). J2x had an overall mean change significantly different from zero. C-terminal telopeptides of type I collagen did not change significantly during the 8 wk. The data demonstrate that the bone of young adult males does respond to a high-impact exercise. In addition, compared with completing all plyo-jumps in one session, the use of recovery periods between exercise sessions on the same day may result in positive changes in bone turnover, indicative of an osteogenic effect. The beneficial impact of the OI and how it can be used to design programs to influence bone turnover still remain to be determined.

Effects of Alendronate on Bone Metabolism in Glucocorticoid-Induced Osteoporosis Measured by18F-Fluoride PET: A Prospective Study

Osteoporosis represents a significant side effect of glucocorticoid therapy, and alendronate has been reported to prevent this glucocorticoid-induced osteoporosis. Functional imaging with (18)F-fluoride PET allows quantitative analysis of bone metabolism in specific skeletal regions. However, only a few studies have quantitatively determined bone turnover and metabolism in glucocorticoid-induced osteoporosis by radiologic imaging techniques including PET. The aim of this study was to examine changes in regional bone remodeling and turnover as measured by (18)F-fluoride PET, the relationship between these measured changes and conventional bone metabolism parameters, and the effect of alendronate treatment. The study group consisted of 24 postmenopausal women (mean age, 59.7 y) who had various diseases, excluding rheumatoid arthritis, and had been treated with 10 mg or more of oral glucocorticoids (prednisolone equivalent) per day for more than 6 mo. Treatment with 5 mg of alendronate per day began at the time of study entry and continued for 12 mo. (18)F-fluoride PET was performed at baseline, 3 mo, and 12 mo to determine localized bone turnover, and the results were compared with other bone metabolism parameters. Lumbar spine standardized uptake values (SUVs) were significantly lower (P < 0.05) in the osteoporotic group (T-score < or = -2.5) than in the group that was healthy or osteopenic (T-score > -2.5). Patients treated with alendronate for 12 mo exhibited significant decreases in serum bone-specific alkaline phosphate (P < 0.05), urinary N-telopeptide for type I collagen (P < 0.01), lumbar spine SUV (P < 0.01), and femoral neck SUV (P < 0.01) in association with a gradual increase in bone mineral density (BMD) of the lumbar spine relative to the baseline value (P < 0.05). Although there was a significant correlation between BMD and SUV in the lumbar spine at baseline (P < 0.05), there was no correlation between the 2 variables at 12 mo of treatment with alendronate. Alendronate treatment resulted in significant decreases in bone metabolism and turnover in the lumbar spine. It also led to an increase in BMD of the lumbar spine in patients with glucocorticoid-induced osteoporosis. Our findings suggest that antiresorptive therapy has a direct bone-metabolism effect on skeletal kinetics in glucocorticoid-induced osteoporosis at the clinically important site of the lumbar spine.

High bone matrix turnover predicts blood levels of lead among perimenopausal women

Skeletal bone is the primary endogenous source of lead in circulating blood, particularly under conditions of accelerated bone turnover and mineral loss, such as pregnancy and postmenopausal osteoporosis. We studied the influence of bone turnover rate on the release of lead from bone in 1225 female farmers from 5 districts in Japan. We collected peripheral blood and urine samples and medical nutritional information, and measured forearm bone mineral density (BMD). We found that blood lead levels in perimenopausal women were highest among all groups studied. Analysis of data for subjects grouped by level of markers of bone metabolism suggested that, in perimenopausal women, blood lead levels were higher in groups with high levels of N-telopeptide cross-linked collagen type I (NTx) and high levels of bone-specific alkaline phosphates (BALP) or osteocalcin (OC) compared with groups with low NTx and low BALP or OC levels. Linear multivariate models showed that markers of bone turnover were significantly positively related to blood lead levels. These results provide evidence that high bone turnover rates increase the release of lead stored in bone into the circulation. It is likely that markers of bone metabolism can be used to predict blood lead levels.

Successful off-label use of cinacalcet HCl after standard therapy failure in a young man with pseudohypoparathyroidism Type 1b and vitamin D intoxication sequelae

We describe the case of a young man with pseudohypoparathyroidism Type 1b--a rare genetic disorder characterized by end-organ resistance to parathormone (PTH)--and vitamin D intoxication sequelae due to inappropriate and poorly monitored calcitriol treatment in his adolescence, who could no longer be successfully treated by standard vitamin D treatment alone. Off-label administration of cinacalcet HCl, a calcimimetic approved for the treatment of secondary hyperparathyroidism, together with the vitamin D analog dihydrotachysterol, however, proved successful in controlling parathormone (PAH), bone-specific alkaline phosphatase (BAP), serum calcium, and phosphate levels.

Secondary osteoporosis in long‐term bedridden patients with cerebral palsy

The aim of the present paper was to investigate 20 pediatric patients with cerebral palsy and secondary osteoporosis and consider the efficacy, influence and index of treatment. A total of 10 boys and 10 girls, age 1-16 years (mean 7.6 years) with secondary osteoporosis and cerebral palsy treated for 6 months, were studied. Bone mineral density (BMD) was measured. The bone turnover markers were measured just before and 4 months after treatment or at the time of early discontinuation of treatment. The treatment was classified into two groups: vitamin D (alfacarcidol) only; and with bisphosphonate (risedronate). Monotherapy with alfacarcidol was effective for secondary osteoporosis in children, but when used in combination with risedronate it was even more effective in improving BMD. In the two groups, bone-specific alkaline phosphate (BAP) decreased from pretreatment to post-treatment assessment in all but one case, but there was no significant correlation in the difference in DeltaBAP with DeltaBMD. DeltaBAP assumed changes in BAP in treatment either before or after, and DeltaBMD also assumed changes in BMD. N-telopeptides of type I collagen (NTX)/Cr decreased in all cases. The correlation of DeltaNTX/Cr with DeltaBMD was not significant. The therapy and its efficacy did not correlate to the patients' age, sex, medicine regimen or enteral nutrition. Risedronate therapy is effective for patients presenting with secondary osteoporosis with cerebral palsy. Moreover, it is desirable to treat patients more aggressively from the early stage because risedronate is not affected by the patients' other factors.

Effects of 22‐Oxacalcitriol and Calcitriol on PTH Secretion and Bone Mineral Metabolism in a Crossover Trial in Hemodialysis Patients With Secondary Hyperparathyroidism

The purpose of this crossover comparison study is to elucidate the differences between the effects of a novel calcitriol analog, 22-oxacalcitriol, and calcitriol on parathyroid hormone (PTH) and bone mineral metabolism in hemodialysis patients with secondary hyperparathyroidism (SHPT). Twenty-three patients with moderate to severe SHPT were included in a random 2 x 2 crossover trial with two vitamin D analogs (12 weeks for each treatment). Two patients withdrew during the run-in period for personal reasons. Serum electrolyte, bone metabolic marker, intact PTH (iPTH) and whole PTH (wPTH) levels were measured periodically. The primary endpoint measure was a decrease in serum iPTH level, and the secondary outcome measures included changes in serum calcium (Ca), phosphate (P), and metabolic bone marker levels. Both treatments decreased iPTH and wPTH levels by similar degrees. Serum Ca, P, and Ca x P product levels at the end of each treatment were comparable and the frequencies of hypercalcemia and hyperphosphatemia were also similar during each treatment period. 22-Oxacalcitriol significantly decreased the levels of bone metabolic markers, namely, bone-specific alkaline phosphate, intact osteocalcin, pyridinoline, and cross-linked N-telopeptide of type I collagen, after a 12-week treatment. In contrast, calcitriol did not change any of the levels of bone metabolic markers. The present study showed that 22-oxacalcitriol is equally effective for PTH suppression, and Ca and P metabolism. In addition, 22-oxacalcitriol might have putative actions on bone remodeling independent of its PTH suppression. Further study is necessary to confirm the effects of 22-oxacalcitriol on bone metabolism in SHPT.

Evaluation of different bone markers in hemodialyzed patients

Background Routinely, nephrologists rely on different biochemical markers like intact PTH (iPTH), bone-specific alkaline phosphatase (BALP), plasmatic calcium and phosphate. The aim of the present study was to evaluate different other bone markers like N-terminal propeptide of type 1 procollagen (P1NP), active isoform 5b of the tartrate-resistant acid phosphatase (TRAP 5b) and β-crossLaps® (CTXS) as well as full-length PTH (wPTH), presumed non-(1–84) PTH, and their ratio in the diagnosis of renal osteodystrophy with high and low turnover. We also determined 25 hydroxyvitamin D (25VTD), 1–25 dihydroxyvitamin D and homocystein (HCY). Methods We performed those parameters on 73 patients with end-stage renal disease according to the manufacturers' instructions. Results There were very strong correlations between the bone markers concentrations, particularly between BALP and P1NP ( r = 0.953). We did not observe any correlation between the ratio whole PTH/non-(1–84) PTH and any of the usual bone markers. This ratio was significantly ( p < 0.05) higher in low and high bone turnover patients than in normal patients according to the K/DOQI. We found a correlation between low levels of 25VTD and high levels of HCY. Conclusions BALP offers the best clinical and analytical profile as the easier marker of choice in hemodialyzed patients for the diagnosis of bone disease.

Currently used growth-promoting treatment of children results in normal bone mass and density. A prospective trial of discontinuing growth hormone treatment in adolescents.

The need for continued GH replacement in patients with childhood-onset GH deficiency (GHD) into adulthood has been recognized. The consequences of discontinuing GH treatment on bone mineralization in adolescent patients with GHD and short stature were examined over a period of 2 years. Forty adolescents (aged 16-21 years) treated with GH for more than 3 years and 16 closely matched healthy controls were studied. After a baseline visit, GH treatment was discontinued. The patients were then re-examined with the same protocol after 1 and 2 years. Twenty-one patients had continuing severe GHD into adulthood, while 19 patients were regarded as having sufficient endogenous GH secretion (GHS). At baseline, there were no differences between the groups in total bone mineral content (BMC) or bone mineral density (BMD). After 2 years without GH treatment, BMC increased similarly in the GHD and GHS groups. BMC of the lumbar spine (L2-L4) increased only in the GHD group. Lumbar spine BMD increased in the GHD and the GHS groups. No changes were observed in the femoral neck region. Biochemical measurements showed that carboxy-terminal cross-linked telopeptide of type I collagen (ICTP) and bone specific alkaline phosphates (ALP) were higher in the GHD and GHS groups at baseline compared with controls. Osteocalcin, carboxy-terminal propeptide of type I procollagen (PICP), ICTP and ALP decreased during the 2 years off treatment in both the GHD and GHS groups. PICP was also lower after 2 years in the GHD group compared with both the GHS group and controls. After discontinuation of GH therapy in adolescents at or near final height, there was a continued increase in BMC and BMD both for adolescents with growth hormone deficiency and for those classified as growth hormone sufficient. These groups did not differ from controls at baseline or after 2 years. In the growth hormone deficiency group, biochemical markers for bone formation decreased to levels below those in the growth hormone sufficient and healthy control groups. Although the number of patients and controls in this study were small, the results indicate that the present treatment of Swedish GH-deficient children to final height results in normal BMD.