Total Alkaline Phosphatase Concentrations Research Articles

Characteristics of Early Paget's Disease in SQSTM1 Mutation Carriers: Baseline Analysis of the ZiPP Study Cohort.

Mutations in SQSTM1 are strongly associated with Paget's disease of bone (PDB), but little is known about the clinical characteristics of those with early disease. Radionuclide bone scans, biochemical markers of bone turnover, and clinical characteristics were analyzed in SQSTM1 mutation carriers who took part in the Zoledronic acid in the Prevention of Paget's disease (ZiPP) study. We studied 222 individuals, of whom 54.9% were female, with mean ± SE age of 50.1 ± 0.6 years. Twelve SQSTM1 mutations were observed, including p.Pro392Leu, which was present in 141 of 222 (63.5%) subjects. Bone scan examination revealed evidence of PDB in 20 subjects (9.0%), ten of whom (50%) had a single affected site. Participants with lesions were older than those without lesions but the difference was not significant (53.6 ± 9.1 versus 49.8 ± 8.9; p = .07). The mean age of participants with lesions was not significantly different from the age at which their parents were diagnosed with PDB (55 years versus 59 years, p = .17). All individuals with lesions were asymptomatic. Serum concentrations of total alkaline phosphatase (ALP) normalized to the upper limit of normal in each center were higher in those with lesions (0.75 ± 0.69 versus 0.42 ± 0.29 arbitary units; p < .0001). Similar findings were observed for other biochemical markers of bone turnover, but the sensitivity of ALP and other markers in detecting lesions was poor. Asymptomatic PDB is present in about 9% of SQSTM1 mutation carriers by the fifth decade. Further follow-up of this cohort will provide important information on the natural history of early PDB and its response to treatment. © 2020 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research.

Loss-of-Function Mutations in the ALPL Gene Presenting with Adult Onset Osteoporosis and Low Serum Concentrations of Total Alkaline Phosphatase.

ABSTRACTHypophosphatasia (HPP) is a rare inherited disorder characterized by rickets and low circulating concentrations of total alkaline phosphatase (ALP) caused by mutations in ALPL. Severe HPP presents in childhood but milder forms can present in adulthood. The prevalence and clinical features of adult HPP are poorly defined. The aim of this study was to evaluate the prevalence and clinical significance of low serum total alkaline phosphatase (ALP) levels in a clinic‐based population of adult osteoporotic patients. We searched for patients with low ALP in a cohort of 3285 patients referred to an osteoporosis clinic over a 10‐year period and performed mutation screening of ALPL in those with low ALP (≤40 U/L) on two or more occasions. These individuals were matched with four clinic controls with a normal ALP. We also evaluated the prevalence of low ALP and ALPL mutations in 639 individuals from the general population from the same region. We identified 16/3285 (0.49%) clinic patients with low ALP and 14 (87.5%) had potentially pathogenic variants in ALPL. Eight of these individuals were heterozygous for mutations previously described in HPP and 2 were heterozygous for novel mutations (p.Arg301Trp and p.Tyr101X). These mutations were not found in clinic controls or in the general population. Eight patients with low ALP, including 4 with ALPL mutations, were treated with bisphosphonates for an average of 6.5 years. In these individuals, the rate of fractures during treatment was comparable to that in normal ALP clinic controls who were treated with bisphosphonates. We conclude that heterozygous loss‐of‐function mutations in ALPL are common in osteoporosis patients with low ALP. Further studies are required to determine how best these individuals should be treated. © 2019 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research.

Catechin-rich oil palm leaf extract enhances bone calcium content of estrogen-deficient rats

ObjectivePostmenopausal estrogen deficiency often causes bone density loss and osteoporosis. This study evaluated the effects of an oral administration of oil palm leaf extract (OPL) on bone calcium content and structure, bone density, ash weights, and serum total alkaline phosphatase (T-ALP) of estrogen-deficient ovariectomized (OVX) rats. MethodsFemale Sprague-Dawley rats were divided into five experimental groups: 1) intact (normal control); 2) ovariectomized (OVX control), and OVX rats supplemented with 3) 2% (w/v) green tea (OVX + GT), 4) OPL 150 mg/kg of body weight, or 5) OPL 300 mg/kg of body weight in the drinking water. ResultsAfter 3 mo, the OVX control rats had significantly decreased femur and tibia masses (−5% and −3%, respectively), ash (−15% and −10%), calcium content (−0.5% and −2.7%), and bone density and T-ALP concentrations (−40%) compared with intact rats. The catechin-rich OPL dose dependently increased the OVX bone density and structure, femur and tibia masses (by +8% and +12% respectively), ash (by +30% and +20% respectively), calcium (by +3% and +5%), and T-ALP concentrations (by +76%) compared with the OVX rats. The increases by OPL were higher than that in OVX + GT and control intact rats. ConclusionThe catechin-rich OPL increased the bone mass in estrogen-deficient rats by increasing osteoblast activities to higher levels than in normal rats and those supplemented with GT. This was shown by the modulation of serum T-ALP levels, bone calcium content, total mineral content, and bone histologic structure. The OPL is a potential inexpensive ingredient for protection against osteoporosis and influences bone metabolism by encouraging bone formation.

Influence of benzoic acid and phytase in low-phosphorus diets on bone characteristics in growing-finishing pigs1

In 2 simultaneous experiments (Exp. 1 and Exp. 2), the effects of benzoic acid (BA) and phytase (Phy) in low-P diets on bone metabolism, bone composition, and bone stability in growing and growing-finishing pigs were examined. Experiment 1 was conducted with 16 crossbred gilts in the BW range of 25 to 66 kg of BW, whereas in Exp. 2, 32 crossbred gilts (25 to 108 kg of BW) were used. All pigs were individually housed in pens and restrictively fed 1 of 4 diets throughout the experiment. Total P content of the wheat-soybean diets was 4 g/kg (all values on an as-fed basis). The experimental diets were 1) unsupplemented control diet; 2) control diet with 0.5% BA; 3) Phy diet with 750 Phy units (FTU) of Phy/kg and no BA; and 4) PhyBA, control diet with 750 FTU of Phy/kg and 0.5% BA. Blood samples were taken at the beginning of the experiment, wk 3 (only for pigs in Exp. 1), wk 6, and before slaughter to determine P and Ca in serum and concentrations of total alkaline phosphatase, serum crosslaps (marker for bone resorption), and osteocalcin (marker for bone formation). Ash, P, and Ca contents of bones and bone stability were examined using the left metatarsal bones and tibia of the pigs after slaughter. Benzoic acid did not influence any of the blood variables (P > 0.09). The addition of Phy increased (P < or =0.03) P concentration in serum from 2.71 +/- 0.08 to 3.03 +/- 0.07 mmol/L at wk 3 and content of serum crosslaps from 0.39 +/- 0.02 to 0.45 +/- 0.02 ng/mL at wk 6 and decreased (P < 0.05) osteocalcin at wk 6 by 160 ng/mL. No long-term effect of diets on serum mineral concentrations, alkaline phosphatase, and bone markers in serum could be detected. Benzoic acid negatively affected (P < or = 0.03) Ca content in bones and distal bone mineral density, especially in the younger pigs. In the control diet with 0.5% BA and the control diet with 750 FTU of Phy/kg and 0.5% BA, the CA content in bones and distal bone mineral density were reduced by 6 and 11%, respectively. Throughout the whole growing and finishing period, Phy increased (P < or =0.02) ash, P, and Ca contents in bones by 29.4, 4.8, and 11.6 g/kg of DM, respectively. Bone mineral density and bone mineral content were greater in diets with Phy (P < or = 0.03), as well as breaking strength of tibia (+22%) and metatarsal bones (+27%; P < 0.01). The results of this study indicate that for a healthy skeleton, BA should not be used in low-P diets without the addition of Phy.

Changes in total alkaline phosphatase level after hip fracture: comparison between femoral neck and trochanter fractures

BackgroundBiochemical bone metabolic markers are affected by fractures, and total alkaline phosphatase (ALP) is considered one of the bone formation markers. Only a few reports have dealt with changes in bone formation markers during the healing process of bone fragility hip fractures. Despite the difference in the amount of callus formation and bone fusion rate, no significant differences in longitudinal change of total ALP between femoral neck and trochanter fracture have been reported. MethodsA total of 69 osteoporotic patients with femoral neck or trochanter fracture whose serum concentrations of total ALP were examined at least four times at six periodic examination points (1, 2, 3, 4, 6, and 8weeks after surgery) and whose state of bone union was obtained within 24weeks after surgery were selected for this retrospective study. The characteristic longitudinal change of total ALP during the healing process was shown, and the possibility of total ALP as a predictive factor for the state of osteosynthesis of hip fractures is discussed. ResultsChanges in the total ALP level according to the healing process were similar for femoral neck and trochanter fractures. The concentration of total ALP rose to a maximum at 3weeks after surgery and then gradually decreased for both fractures. However, the range of change was significantly greater for trochanter fractures than for femoral neck fractures. For trochanter fractures, total ALP decreased from 3 to 6weeks after surgery in all but one patient. ConclusionsIncreases in the concentration of total ALP after surgery and the subsequent decreases may reflect the normal healing process. A significant difference in the changes of total ALP after surgery between femoral trochanter and neck fractures was shown. Periodic measurement of total ALP might be useful for obtaining information on the osteosynthesis state.

Unilateral and bilateral vasectomy in the dog: alkaline phosphatase as an indicator of tubular patency.

The objective of this research was to use a model of unilateral and bilateral occlusion of the ductus deferens in the dog to study the use of alkaline phosphatase (AP) as an indicator of tubular patency. Seven healthy cross bred dogs weighing 10-15 kg BW with normal spermiogram and AP concentrations in semen were used. From each dog, three semen samples were obtained before (intact) and after right (unilateral) and left (bilateral) vasectomy. The AP concentrations were measured in duplicates by a colorimetric method in each of the three fractions (first, second (sperm-rich), third) of each ejaculate. In addition, a macroscopic and microscopic evaluation of each ejaculate was carried out to assure its quality. Data were analysed by least squares analysis of variance using SAS(R). In intact and unilateral vasectomized dogs, 96.6% of AP measured in semen corresponded to the second sperm-rich fraction whereas 1.53 and 1.83% corresponded to the first and third fractions respectively. Total AP concentrations (first and second and third fraction) in vasectomized dogs were lower than in intact animals (19.857 vs 2284.431 +/- 4.347 UAL; p < 0.001). AP concentrations were much lower in bilateral than in unilateral vasectomized dogs (142 vs 39.572 +/- 4.347 UL, p < 0.001). In summary, AP concentrations in semen can be used as an early indicator of unilateral or bilateral lack of patency of the epididymal and deferent ducts in the dog.

A new assay method that detects only intact osteocalcin. Two-step non-invasive diagnosis to predict adynamic bone disease in haemodialysed patients.

We studied the usefulness of a new assay method that detects only the intact human osteocalcin molecule in haemodialysed patients. Iliac bone biopsy specimens obtained from 62 haemodialysed patients were analysed. Bone formation rates (BFR/BS) correlated positively with serum intact osteocalcin concentrations (n=62), osteocalcin concentrations assayed by a conventional method (n=31), parathyroid hormone (PTH) concentrations (n=62), and total alkaline phosphatase concentrations (r=0.602, 0. 588, 0.650, and 0.401 respectively). Based on ROC curve and Youden index analysis, the optimal cut-off value to distinguish adynamic bone disease from a mild lesion was 195 pg/ml of serum PTH concentration (Youden index=0.233) or 30 ng/ml of serum intact osteocalcin concentration (Youden index=0.628). The optimal cut-off value to distinguish between hyperparathyroid bone and a mild lesion was 455 pg/ml of serum PTH level (Youden index=0.63) or 50 ng=ml of serum intact osteocalcin concentration (Youden index=0.634). Since both ROC curve and Youden index suggested that the serum PTH concentration was not a good marker to distinguish adynamic bone from a mild lesion or hyperparathyroid bone, we designed a two-step procedure. The first step was the diagnosis of adynamic bone (cut-off: 65 pg/ml) or hyperparathyroid bone (cut-off: 455 pg/ml) according to serum PTH concentration. In a second step, we assessed serum intact osteocalcin concentration in patients with serum PTH concentrations between 65 and 455 pg/ml. The cut-off values for adynamic and hyperparathyroid bone in this diagnostic approach were 30 and 70 ng/ml respectively. As a result, 49 out of 62 patients were diagnosed properly. The Youden index of this two-step diagnosis was 0.527 and 0.661 for adynamic bone and hyperparathyroid bone respectively. Sensitivity markedly improved to 94.4% and 96.2% for adynamic bone and hyperparathyroid bone respectively, without sacrificing specificity (84.0 and 88.8% respectively). Measurement of serum intact osteocalcin concentration is useful for the diagnosis of adynamic bone in haemodialysed patients. A two-step procedure involving also simultaneous measurement of serum PTH concentration further improved the sensitivity of each individual marker while maintaining specificity.

Longitudinal study of calcium metabolism in male puberty. I. Bone mineral content, and serum levels of alkaline phosphatase, phosphate and calcium.

With the purpose of studying calcium metabolism at the growth spurt phase in puberty, bone mineral content (BMC) of the forearm, and serum concentrations of total alkaline phosphatase, phosphate, and calcium were determined in 36 boys every three months for about 2 years. BMC increased 35% throughout the study age period of 10.6 to 14.6 years, with a maximal rate between 12.8 and 13.8 years. In relation to growth velocity BMC rose steepest during the 12 months around peak height velocity (PHV) (p less than 0.001) and showed a progressive increase from 3 months before the first pubic hair stage (PH2) to PH4 (p less than 0.001). Serum alkaline phosphatase increased by a total of 55% throughout the age period with a diminished rate of increase from 13.5 to 14 years, around the PHV, and from PH3 to PH4.