Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.1.3.1 (alkaline phosphatase)
47,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We tested the hypothesis that biomarkers of bone resorption are increased in hyperprolactinemic amenorrheic patients with estrogen (E) deficiency, augmenting the possible risk of developing osteoporosis. Fifty hyperprolactinemic patients with amenorrhea of more than 12 months and with low serum E2, as well as 30 healthy fertile women (controls), matched for age and body mass index, participated in this study. Bromocriptine was administered orally to hyperprolactinemic patients and blood and urine samples were collected before and 12 weeks after treatment. Serum osteocalcin (OC) and bone-specific alkaline phosphatase (B-ALP), reflecting bone formation, and urinary deoxypridinoline (D-Pyr) and N-telopeptide of type 1 collagen (NTX) excretion, reflecting bone resorption, were measured using direct immunoassays. Hyperprolactinemic patients had higher (p < 0.0005) levels of all the biomarkers compared to control values: (OC, 22+/-1.2 [SE] vs. 14+/-.99 ng/ml (+57 %); B-ALP, 14.2+/-0.7 vs. 7.5+/-0.8 ng/ml (+89 %); D-Pyr, 8.8+/-0.6 vs. 3.2+/-0.3 nmol/mmol creatinine (+175%) and NTX, 65+/-5.1 vs. 25+/-3.2 nmol bone collagen equivalent (BCE)/mmol creatinine (+160%)). These results were associated with significantly decreased lumbar spine bone mineral density (LS-BMD), measured by dual energy X-ray absorptiometry (DEXA). Treatment of hyperprolactinemia with bromocriptine restored normal values of bone formation and resorption markers. In conclusion, hyperprolactinemia with estrogen deficiency exhibits a significant increase of bone resorption which is associated with a significant decrease of LS-BMD. These changes may subject the patient to the possible risk of developing osteoporosis.
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PMID:Biomarkers of bone turnover and bone mineral density in hyperprolactinemic amenorrheic women. 1036 15

Among pathologies prevalent in western societies, anorexia nervosa has increased over the last decade. Its effects on bone mass need to be defined, and prognostic factors, either clinical or biochemical, could aid clinicians in individual patient management. To determine which clinical and/or biochemical parameters could be related to bone mass status in adolescent female anorexia nervosa patients, 73 female patients were classified according to different stages of their illness and studied in terms of clinical and biochemical parameters and bone densitometric mineral content at lumbar spine. Patients (age 17.2 +/- 1.7 y, mean +/- SD) with Tanner pubertal stage 5, regular menstruation for more than 3 mo before the onset of secondary amenorrhea, and diagnosed with anorexia nervosa were consecutively studied and classified in three clinical situations: I) active phase (34 patients): undernourished and amenorrheic; II) weight recovered but still amenorrheic (20 patients); III) fully recovered (19 patients). Clinical data were recorded at the time of bone density measurement, concomitant with blood sample extraction for study of IGF-I, IGF-binding protein 3 (IGFBP-3), IGFBP-1, estradiol, sex hormone-binding globulin, dehydroepiandrosterone sulfate, prealbumin, amino-terminal propeptide of procollagen III, osteocalcin, bone alkaline phosphatase, carboxy-terminal propeptide of procollagen I, amino-terminal propeptide of procollagen I, carboxy-terminal telopeptide of collagen I, 25-OH-vitamin D, 1,25(OH)(2)-vitamin D, and parathormone. In addition, a 24-h urine collection was made for cortisol, GH, deoxypyridinoline, amino-terminal telopeptide of collagen I, and calcium and creatinine content analysis. IGF-I, estradiol, and biochemical bone formation markers were higher and IGFBP-1, sex hormone-binding globulin, and biochemical bone resorption markers were lower in the weight-recovered stages (stages II and III) compared with the active phase (stage I). Bone formation markers correlated positively with body mass index SD score and IGF-I, whereas bone resorption markers correlated negatively with body mass index SD score and estradiol. Although no statistically significant differences regarding lumbar spine bone mineral density SD score values were recorded among the three stages of the illness, the proportion of osteopenic patients was clearly lower among stage III patients. The actual bone mineral density was inversely related to the duration of amenorrhea and directly related to duration of postmenarcheal menses before amenorrhea. In addition, a subset of osteopenic patients (five of 19) in the fully clinically recovered group with accelerated bone turnover was identified. Normal circulating estrogen level exposure time predicts actual bone mineral density at lumbar spine in young adolescent anorexia nervosa patients. In addition to psychiatric and nutritional interventions, estrogen-deprivation periods must be shortened to less than 20 mo. Patients remaining osteopenic at full clinical recovery require additional follow-up studies.
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PMID:Clinical and biochemical determinants of bone metabolism and bone mass in adolescent female patients with anorexia nervosa. 1191 36

In order to investigate clinico-pathological problems of lactational amenorrhea, a follow-up study was undertaken in 110 women from the date of childbirth up to the end of the first postnatal year. Analysis of the 110 cases showed that in 12 cases (10.9%) regular menstruation commenced just after the puerperium, irrespective of lactation. In the remaining 98 cases, duration of amenorrhea varied from 7 weeks to a little more than 1 year. Even with prolonged lactation varying from 24 weeks to 1 year, menstruation was restored in 89 cases (80.9%) by the end of 24 weeks. Only in 12 cases (10.9%), menstruation failed to resume even at the end of 1 year. Irregularity of cyclical bleeding was more frequent when menstruation reappeared before 24 weeks. Menstruation did reappear earlier in nonlactating than in lactating women. It was determined that ovarian hormones play little part in the phase of repair and restoration of the endometrial structure up to the end of 3 weeks after childbirth. After the puerperium, estrogen activity is restored and well maintained in 96.1% of the cases of lactational amenorrhea. Evidence of ovulation as indicated by secretory endometrium, glycogen activity, and lowering of alkaline phosphatase activity could be demonstrated in 11.8% of cases during lactational amenorrhea. It was found that ovulation is common in cases where menstruation is resumed before 13 weeks. Lactational amenorrhea, especially within this period, should not be considered as a safe period.
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PMID:A clinico-pathological study of lactational amenorrhoea. 1230 62

Changes in bone turnover, and consequent bone loss and recovery during lactation and the postweaning period, are likely modulated by varying estrogen levels inherent in these time periods. To address this question we measured serum biochemical markers of bone formation (bone-specific alkaline phosphatase, amino-terminal propeptide of type I procollagen, osteocalcin), of bone resorption (type I collagen carboxy-terminal telopeptide), and serum female sex hormones (estradiol, luteinizing hormone and follicle-stimulating hormone) in 32 healthy mothers prospectively after delivery, 3 months postpartum, after postpartum amenorrhea and 1 year after resumption of menses. During postpartum amenorrhea (mean 5.7, SD 2.9 months) bone mineral density decreased significantly, some 2% at the lumbar spine and some 3% at the femoral neck, but subsequently recovered completely at the former site and partially at the latter. Bone turnover marker levels were elevated at parturition and still at the end of postpartum amenorrhea. Subsequent to parturition the bone resorption marker level showed a decreasing trend while the formation marker levels continued increasing, and eventually coincided with the resorption level within the very first months postpartum. Both lactation and hormonal status modulated bone turnover marker levels. Maternal age was positively associated with increased bone turnover. Interestingly, higher parity and longer history of previous lactation were associated with lower bone turnover marker levels postpartum as compared with previously nulliparous women of the same age. The regression models explained typically some 20-30% of the variability in the bone turnover marker levels. The dynamic pattern in bone turnover is dissimilar to that occurring at menopause and it indicates that the bone loss most likely occurs in the beginning of postpartum period. It also seems that estrogen has a specific influence on bone turnover only during the first months of lactation.
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PMID:Bone turnover markers during lactation, postpartum amenorrhea and resumption of menses. 1273 Jul 83

This multicenter, double-blind, placebo-controlled, randomized study of 45 patients evaluated the short-term effects of an oral contraceptive [Ortho Tri-Cyclen, 180-250 micro g of norgestimate (NGM) and 35 microg of ethinyl estradiol (EE)] on biochemical markers of bone resorption, formation, and osteoprotegerin in young women (mean age +/- SD, 26.5 +/- 6.3 yr) with hypothalamic amenorrhea and osteopenia. Body fat, endocrine, and cognitive function were evaluated as secondary endpoints. Biomarkers of bone metabolism were measured at baseline and after three cycles of NGM/EE or placebo. There were significant decreases in mean values of N-telopeptide [mean (SD), -13.4 (13.4) vs. 1.2 (23.8) nmol bone collagen equivalents (BCE)/mmol creatinine (Cr); P = 0.001] and deoxypyridinoline [-1.2 (2.9) vs. -0.5 (1.5) nmol deoxypyridinoline/mmol Cr; P = 0.021] as well as significant decreases in bone specific alkaline phosphatase [-5.1 (3.5) vs. 0.4 (3.1) ng/ml; P < 0.001], osteocalcin [-5.9 (3.6) vs. -2.9 (3.7); P = 0.016], and procollagen of type I propeptide [-35.2 (44.6) vs. -0.2 (30.0) ng/ml; P = 0.025], but not osteoprotegerin [0.39 (1.46) vs. -0.2 (0.49) pmol/liter; P = 0.397] in the NGM/EE vs. placebo group. There were no significant differences between groups with respect to changes in cognitive function, mood, body weight, body mass index, body fat, percentage of body fat, and all endocrine levels except FSH, [-3.7 (3.8) vs. -0.6 (2.1) IU/liter; P < 0.001, NGM/EE vs. placebo]. No serious adverse events were reported in either group. These results suggest that NGM/EE decreases bone turnover in osteopenic premenopausal women with hypothalamic amenorrhea. Further studies are needed to determine whether estrogen will increase bone density in this population.
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PMID:Effects of a triphasic combination oral contraceptive containing norgestimate/ethinyl estradiol on biochemical markers of bone metabolism in young women with osteopenia secondary to hypothalamic amenorrhea. 1291 50

Osteoporosis in hemodialysis patients is associated with high morbidity and mortality and, although extensively studied by noninvasive methods, has never been assessed through bone biopsy. The aim of this study was to use histomorphometry to evaluate osteoporosis and identify factors related to its development in hemodialysis patients. We conducted a cross-sectional study involving 98 patients (35 women and 63 men; mean age: 48.4 +/- 13 years) on hemodialysis for 36.9 +/- 24.7 months. Patients were submitted to transiliac bone biopsy with double tetracycline labeling. The bone metabolism factors ionized calcium, phosphorus, bone alkaline phosphatase, deoxypyridinoline, intact parathyroid hormone, and 25(OH) vitamin D were evaluated, as were the bone remodeling cytokines osteoprotegerin (OPG), soluble receptor-activator of NF-kappabeta ligand (sRANKL) and tumor necrosis factor-alpha (TNF)alpha. Osteoporosis was defined as trabecular bone volume (BV/TV) greater than 1 s.d. below normal (men <17.4%; women <14.7%). Forty-five patients (46%) presented osteoporosis, which was correlated with white race. We found BV/TV to correlate with age, OPG/sRANKL ratio, TNFalpha levels, and length of amenorrhea. In multiple regression analysis adjusted for sex and age, length of amenorrhea, white race, and OPG/sRANKL ratio were independent determinants of BV/TV. Histomorphometric analysis demonstrated that osteoporotic patients presented normal eroded surface and low bone formation rate (BFR/BS). Osteoporosis is prevalent in hemodialysis patients. Low BFR/BS could be involved in its development, even when bone resorption is normal. Cytokines may also play a role as may traditional risk factors such as advanced age, hypogonadism, and white race.
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PMID:Osteoporosis in hemodialysis patients revisited by bone histomorphometry: a new insight into an old problem. 1661 34

Anorexia nervosa (AN) is a life-threatening eating disorder characterized by an inability to maintain a normal body weight and amenorrhoea, often associated with osteoporosis and increased risk of fragility fractures. Bone metabolism, including markers of bone turnover (serum total alkaline phosphatase, bone alkaline phosphatase [bone AP], osteocalcin [OC] and type I collagen C-telopeptide breakdown products [sCTX]) and bone mineral density (BMD) by dual energy X-ray absorptiometry (DXA) at the spine and at the hip, were evaluated in 55 consecutive women with AN undergoing a 3-month intensive nutritional rehabilitation program. The control group was constituted of 25 healthy young medical students. In AN patients body weight increased during the 3-month nutritional program from 37.8+/-5.1 (mean+/-SD) to 51.5+/-4.5 kg. The corresponding BMI rose to values >17.5 kg/m(2) in all patients. Mean BMD significantly rose by 2.6+/-3.5% and 1.1+/-3.6% at the hip and at the spine, respectively. The markers of bone formation, serum bone AP and osteocalcin, significantly rose by two-folds, while sCTX decreased by 16%. The changes in hip BMD were positively related (p<0.005) to changes in body weight and in bone AP (p<0.02) while the changes in spine BMD were positively related to changes in serum osteocalcin (p<0.05). In the 25 patients who attended the 12-month posttreatment control, mean body weight significantly decreased by 3.6+/-6.0 kg and this was not associated with any significant change in BMD values. In the patients in whom BMI fell again below 17.5 kg/m(2) hip BMD values decreased significantly. On the contrary, in the patients who maintained BMI >17.5 kg/m(2), BMD values continued to rise up to values over the 15-month observation of 4.8+/-6.2 and 7.1+/-12.1 at the spine and hip, respectively. In conclusion, we have demonstrated that substantial gains in weight in women with chronic AN are associated with remarkable increases in BMD at both the hip and the spine. If weight is maintained, the overall improvement approach 1 SD within 1 year. The changes in both weight and BMD are correlated with improvements in bone formation markers and diminutions in a marker of bone resorption.
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PMID:Marked increases in bone mineral density and biochemical markers of bone turnover in patients with anorexia nervosa gaining weight. 1724 Feb 12

The purpose of this cross-sectional study was to assess the extent of and mechanisms involved in bone loss in anorexia nervosa patients. We compared 113 anorexia nervosa patients (mean age 25 +/- 8 years, mean duration of disease 5.7 +/- 6.1 years) with 21 age-matched controls. Mean duration of amenorrhea was 3.2 +/- 4.7 years. We measured serum calcium and phosphate; bone remodeling markers (osteocalcin, bone-specific alkaline phosphatase [BSAP], serum crosslaps [CTX], and carboxyl-terminal telopeptide of type I collagen [ICTP]); follicle-stimulating hormone and luteinizing hormone levels; and estradiol (ultrasensitive assay), cortisol, urinary free cortisol, thyroid function, prolactin, and nutritional factors (insulin-like growth factor I [IGF-I], IGF binding protein 3 [IGFBP3]). In controls, only bone remodeling markers and nutritional factors were measured. Osteodensitometry was also performed on both patients and controls. Weight and body mass index (BMI) were significantly lower in anorexia nervosa patients than in controls (P < 0.0001). No significant differences were observed in biological indicators except for IGF-I, which was lower in anorexia nervosa patients (0.9 +/- 0.4 UI/mL) than in controls (1.5 +/- 0.4 UI/mL) (P < 0.0001). Densitometric measurements at three sites were significantly lower in anorexia nervosa patients and correlated with duration of disease and amenorrhea and with IGF-I at the hip only (P < 0.01). In the study population, osteoporosis was observed in 24 patients (21%) and osteopenia in 54 patients (48%). Patients with osteoporosis were significantly older and had longer disease and amenorrhea durations; lower weight and BMI; higher alkaline phosphatase, BSAP, and osteocalcin; and lower serum ICTP, IGF-I, and IGFBP3. All of these differences were significant and remained so even after multiple adjustments were made, except for IGF-I (P = 0.21). When multivariate analysis was performed, we found that age at onset of amenorrhea, weight, alkaline phosphatase, urinary free cortisol, and serum estradiol concentration accounted for 54% of the variance in spinal bone mineral density (BMD). Duration of amenorrhea, alkaline phosphatase, and weight explained 46.6% of the variance in femoral neck BMD. Duration of amenorrhea, IGF-I, and ICTP levels accounted for 38.6% of the variance observed in total hip BMD. The etiology of bone loss in patients with anorexia nervosa is multifactorial. Hypoestrogenia alone cannot account for this loss, and nutritional factors, IGF-I concentrations in particular, seem to play an important role.
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PMID:Evaluation of bone loss and its mechanisms in anorexia nervosa. 1766 43

We present a 27-year-old woman with hypoparathyroidism following total thyroidectomy for papillary carcinoma, who presented postpartum during lactation with several vertebral osteoporotic fractures, increase in bone turnover markers, and measurable parathyroid hormone-related protein (PTHrP) levels. Cessations of lactation led to gradual decrease in bone turnover markers and PTHrP and improvement in bone mineral density. Pregnancy- and postpartum-associated osteoporosis is an uncommon condition characterized by the occurrence of fractures during late pregnancy or the puerperium. The patient presented postpartum with severe back pain and multiple vertebral fractures. Metabolic evaluation performed at presentation revealed hypercalcemia, hypercalciuria, increased alkaline phosphatase, vitamin D insufficiency, normal serum protein immunoelectrophoresis, and a detectable level of PTHrP. Serum levels of bone turnover markers were markedly increased. Bone mineral density at the lumbar spine was severely reduced. After cessation of lactation, the PTHrP level became undetectable. Bone turnover markers gradually decreased to normal and bone mineral density improved. Several factors contributed to the reduced bone mass in this patient, including amenorrhea treated with oral contraceptives, suppressive levothyroxine treatment, and lactation of twins with increased PTHrP. Patients with severely reduced bone mass need surveillance during pregnancy and lactation and should possibly consider avoiding breastfeeding. Patients with hypoparathyroidism should temporarily reduce their alphacalcidiol dose while lactating.
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PMID:Severe postpartum osteoporosis with increased PTHrP during lactation in a patient after total thyroidectomy and parathyroidectomy. 2124 37

The aim of this study was to evaluate the effects of 4-year estroprogestagen therapy (EP) on the bone mineral density (BMD) of 16- to 17-year-old girls with functional hypothalamic amenorrhea (FHA, n = 78). Baseline values of hormonal parameters, bone fraction of alkaline phosphatase (BALP), and cross-linked n-telopeptide of type I collagen (Ntx) were taken along with BMD measurements. Follow-up measurements of laboratory parameters were performed after 6 months of EP treatment. BMD was measured on a yearly basis. Six-month treatment resulted in a marked increase in estradiol levels and a significant decrease in BALP and Ntx. The relative increase in BMD was highest after the second year of treatment. Based on the dynamics of BMD changes during the first year of treatment, we identified a subgroup with no or insignificant reactions to the treatment. It was characterized by significantly higher baseline BMD and markedly lower baseline Ntx compared to the patients who responded to 1-year therapy well or extremely well. Further follow-up proved, however, that this subgroup did not differ significantly in terms of the long-term prognosis for BMD normalization. In conclusion, this study showed that EP therapy is effective in the treatment of BMD disorders associated with FHA.
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PMID:Bone mineral density in girls with functional hypothalamic amenorrhea subjected to estroprogestagen treatment--a 4-year prospective study. 2150 Sep 96


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