Alteration in osteoblast activity and nutritional vitamin-D deficiency in non-hypercalcemic malignancy

Summary The biochemical parameters of bone mineral metabolism in patients with nonhypercalcemic malignancy have not been extensively investigated. Therefore, a group of 29 such patients with different types of malignancy was studied. Ten patients received corticosteroids. In the entire group, serum ionized calcium (Ca²⁺), bone gla protein (BGP), 25-hydroxyvitamin D (25OHD), and 1,25-dihydroxyvitamin D (1,25(OH)₂D) were all lower than in age-matched controls, and carboxy-terminal parathyroid hormone (CPTH) was higher. Although both corticosteroid- and noncorticosteroid-treated patients had decreased BGP values, the corticosteroid-treated patients had lower BGP levels than those not on steroids (4.24±0.70 SE vs. 11.50±2.20 ng/ml;P<0.005). Patients on corticosteroids had lower 1,25(OH)₂D values than controls (18.81 ±2.71 vs. 27.83±1.17 pg/ml;P<0.01), whereas those not on corticosteroids had normal 1,25(OH)₂D values. These results suggest that patients with nonhydpercalcemic malignancy have nutritional vitamin-D deficiency and secondary hyperparathyroidism with perhaps corticosteroid-induced suppression of serum 1,25(OH)₂D and BGP. The decreased levels of serum BGP in the nonsteroid-treated patients suggest, in addition, a defect in osteoblast function.     

Hyperparathyroidism is responsible for the increased levels of osteocalcin in patients with normally functioning kidney grafts

Osteocalcin or bone Gla protein (BGP) is the most abundant noncollagenous protein of the skeleton. Serum BGP levels are thought to provide a valuable index of bone formation. We measured serum BGP and other parameters of mineral metabolism in 68 patients with functioning kidney grafts. The duration of the graft ranged from 1 to 131 months (mean 23). Serum BGP was positively correlated with parathyroid hormone (r = 0.56, p less than 0.001). BGP was inversely correlated with glomerular filtration rate (r = -0.44, p less than 0.001) and with the total cumulative dose of corticosteroids received after transplantation (r = -0.26, p less than 0.05). No correlation was observed between BGP and 1,25(OH)2D, nor between BGP and serum aluminum. All patients with increased BGP in the presence of normal renal function had persistent hyperparathyroidism. The activity of the parathyroid glands and corticosteroid treatment seem to be the main pathophysiological factors influencing BGP levels after successful kidney grafting.     

Effect of declining renal function on bone density in aging women

Summary The factors that are responsible for trabecular bone loss in aging women are not completely understood. To evaluate declining renal function as a possible factor, we studied 19 Caucasian women (average age 67) who were from 6 to 41 years postmenopausal. Trabecular bone density was quantitated by computerized tomography of the spine. Serum calcium, phosphorus, and creatinine were normal in all subjects. Creatinine clearance averaged 74 ml/min (range 38–122), decreased with age (r=−0.60,P=0.003), and was inversely related to serum creatinine (r=−0.51,P=0.01). Bivariate regression demonstrated that bone density decreased with age (r=−0.59,P=0.004); controlling for the effect of creatinine clearance weakened this correlation to r=−0.45 (P=0.03); controlling additionally for 1,25-dihydroxyvitamin D [1,25(OH)₂D] and parathyroid hormone (PTH) reduced the correlation coefficient to r=−0.34 (P=0.11). Bone density also decreased in direct proportion to the decrement in creatinine clearance (r=0.44,P=0.03); controlling for the effects of 1,25(OH)₂D and PTH reduced this correlation coefficient to r=0.34 (P=0.11). These results suggest that occult renal insufficiency may contribute to bone loss in aging women, and that this effect may be mediated in part by 1,25(OH)₂D and PTH. In this age group renal function should be assessed by measuring creatinine clearance rather than the serum creatinine concentration since renal insufficiency can be masked by apparently normal circulating creatinine levels.     

Comparison of vitamin D metabolism in early healthy and late osteoporotic postmenopausal women

Summary We studied 20 healthy premenopausal women aged 36.5±4.0 years (mean±1 SD), 123 healthy postmenopausal women aged 50.0±2.4 years, and 103 postmenopausal women aged 65.1±5.6 years with symptomatic osteoporosis (forearm and spinal fracture). Serum levels of vitamin D metabolites [25(OH)D, 24,25(OH)₂D₃, and 1,25(OH)₂D] were compared with (1) bone mass in the forearm (single photon absorptiometry) and in the spine (dual photon absorptiometry); (2) biochemical indices of bone formation (serum alkaline phosphatase, plasma bone Gla protien), and bone resorption (fasting urinary hydroxyproline); and (3) other biochemical estimates of calcium metabolism (serum calcium, serum phosphate, 24-hour urinary calcium, intestinal absorption of calcium). The present study revealed no difference in any of the vitamin D metabolites between the premenopausal women, the healthy postmenopausal women and the osteoporotic women as a group. The concentrations of 1,25(OH)₂D and 25(OH)D were significantly lower in patients with spinal fracture than in those with forearm fracture. In the early postmenopausal women, serum 1,25(OH)₂D was related to forearm bone mass (r=−0.20;P<0.05), intestinal calcium absorption (r=0.18;P<0.05), and 24-hour urinary calcium (r=0.21;P<0.05); serum 25(OH)D was related to spinal bone mass (r=0.23;P<0.01). In the osteoporotic women, serum vitamin D metabolites were not related to bone mass, but 1,25(OH)₂D was related to bone Gla protein (r=0.33;P<0.001), serum phosphate (r=−0.27;P<0.01), and 24-hour urinary calcium (r=0.43;P<0.001). The present study demonstrates that in a population that is apparently not deficient in vitamin D, a disturbance of the vitamin D metabolism is not likely to play a pathogenetic role in early postmenopausal bone loss. Patients with spinal fractures have low levels of vitamin D metabolites, which may aggravate their osteoporosis.     

甲状腺功能异常患者血生化、骨代谢及骨密度特点的临床研究

目的观察甲状腺功能减退症及甲状腺功能亢进症对骨密度以及骨代谢相关指标的影响。方法纳入甲状腺功能减退症女性37例为甲减组,甲状腺功能亢进症女性41例为甲亢组,健康体检女性人员40例为对照组。观察3组甲状腺功能指标血游离三碘甲状腺原氨酸(FT_3)、游离甲状腺激素(FT_4)和高敏感促甲状腺激素(TSH);骨代谢指标血Ca~(2+)、血P~(3+)、1,25-(OH)_2D_3、甲状旁腺激素(PTH)、碱性磷酸酶(ALP)、血清Ⅰ型胶原羧基端吡啶并啉交联肽(ICTP)以及血清骨钙蛋白(BGP)以及左侧股骨颈、正位腰椎1-4(L_(1-4))的骨密度情况。结果甲亢组血清FT_3、FT_4、ALP、BGP、ICTP水平高于对照组(P0.05),甲亢组血清TSH水平低于对照组(P0.05)。甲减组血清TSH水平高于对照组(P0.05),而血清FT_3、FT_4、ALP、BGP、ICTP水平显著低于对照组(P0.05)。甲亢及甲减组L1-4及左股骨颈骨密度显著低于对照组(P0.05)。3组受试者PTH、CT、Ca~(2+)、P~(3+)、1,25-(OH)_2D_3比较无统计学意义(P0.05)。结论甲亢及甲减都可以引起骨量丢失,骨密度降低;主要通过影响骨转化来实现的;应该重视甲状腺功能异常引起的骨密度及骨代谢异常。     

1,25 dihydroxyvitamin D3 modifies cyclosporine-induced bone loss

Summary We have previously shown that cyclosporin A (CsA) produces high bone remodeling with resorption exceeding formation and loss of bone volume in the rat. This may have important clinical implications where CsA is widely used in organ transplantation. 1,25 dihydroxyvitamin D₃ (1,25(OH)₂D₃) is a bone mineralizing hormone which also has immune modifying properties. Consequently, we studied the effect of combined CsA and 1,25(OH)₂D₃ administration over 28 days in four groups of rats. Group A received vehicle (n=10), group B CsA (15 mg/kg) (n=10) alone, group C 1,25(OH)₂D₃ plus CsA (n=15), and group D 1,25(OH)₂D₃ alone (20 ng/100 g) (n=15). Rats were bled periodically at day 0, 7, 14, and 28 and Ca, parathyroid hormone (PTH), 1,25(OH)₂D, osteocalcin (bone Gla-protein, BGP), BUN, and creatinine were measured. Rats were sacrificed on day 28 and bones were examined histomorphometrically. Compared to controls, CsA resulted in significant elevation of BGP and a transient increase in 1,25(OH)₂D with excess bone remodeling and loss of bone volume. 1,25(OH)₂D₃ administration produced hypercalcemia, a significant rise in BGP, with suppression of PTH and increased osteoid volume. Combined therapy prevented the loss of bone volume probably due to increased osteoid tissue and enhanced osteoblast activity. Renal dysfunction, a side-affect of CsA, was not a factor. In conclusion, 1,25(OH)₂D₃ combined with CsA restores bone volume which is accompanied by increases in serum calcium and BGP.     

甲状腺疾病与骨钙素

目的 观察甲亢、甲减患者血清骨钙素（ＢＧＰ）含量,探讨甲状腺功能异常与骨代谢的关系。方法 测定４０例甲亢患者,２０例甲减患者血清ＢＧＰ及甲状腺激素含量,并与３０例正常对照组比较。结果 甲亢患者血清ＢＧＰ含量明显高于正常对照组（Ｐ〈０．０１）,甲减患者血清ＢＧＰ含量明显低于正常对照组（Ｐ〈０．０１）,ＢＧＰ的含量与甲状腺激素（ＦＴ３、ＦＴ４）显著正相关,与ｓＴＳＨ显著负相关,与性别无明显相关。结论     

Changes in Bone and Calcium Metabolism Following Hip Fracture in Elderly Patients

Although hip fracture is one of the most common causes of acute immobilization in elderly patients, little is known about the influence of immobilization on changes in bone and calcium metabolism following this event. We therefore compared serum biochemical indices of bone and calcium metabolism in 20 elderly subjects with hip fracture with those measured in 20 healthy age-matched controls. Rankin scores, a measure of functional dependence with 0 representing independence and 5 representing total dependence, were assigned. We also examined serial changes in these biochemical indices from shortly following the fracture to the early recovery period. Ionized calcium, intact parathyroid hormone (PTH), intact bone Gla protein (BGP), pyridinoline cross-linked carboxyterminal telopeptide of type I collagen (ICTP), 25-hydroxyvitamin D (25-OHD), and 1,25-dihydroxyvitamin D (1,25-[OH]₂D) were measured. One week after the fracture, mean serum concentrations of calcium and ICTP were elevated in correspondence to degree of immobilization (mean Rankin score; 4.4), while serum concentrations of BGP, PTH, 25-OHD, and 1,25-[OH]₂D were depressed. Rankin score (mean: 4.4) correlated positively with ICTP and negatively with BGP at this time. At 2 months, calcium and ICTP elevation decreased and BGP, PTH and 1,25-[OH]₂D were less depressed, coinciding with a decline in Rankin score from 4.2 to 2.2. Indices were further improved at 3 months (mean Rankin score, 1.3), with calcium and BGP returning to normal. We concluded that increased bone resorption, and decreased bone formation, and hypercalcemia are present by 1 week following the hip fracture, and some resorption increase persists for at least 3 months. These changes could explain in part the high risk of another hip fracture. Received: 3 April 2000 / Accepted: 15 December 2000     

老年男性骨质疏松患者血清胰淀素与骨密度及骨转换生化指标的关系

目的探讨老年男性骨质疏松患者血清胰淀素(Amylin)水平的变化及其与骨密度(BMD)及骨转换生化指标的关系。方法采用酶联免疫法(ELISA)测定89例老年男性骨质疏松患者和50例正常男性老年人血清Amylin、骨碱性磷酸酶(BAP)、骨钙素(BGP)、I型胶原氨基末端肽(NTX),采用美国NORLAND XR-46 Excell-plus双能X线骨密度测定仪分别测定正位腰椎(L2-L4)及左侧股骨颈BMD。结果老年男性骨质疏松患者正位腰椎及左侧股骨颈BMD、血清Amylin、BAP、BGP水平较正常男性老年人明显降低(均P<0.01),血清NTX水平较正常男性老年人明显升高(P<0.01)。老年男性骨质疏松患者血清Amylin水平与患者正位腰椎及左侧股骨颈BMD、血清BAP、BGP水平呈明显正相关(r=0.598,r=0.652,r=0.576,r=0.584,均P<0.01),与患者血清NTX水平呈明显负相关(r=-0.673,P<0.01)。结论血清胰淀素水平降低在老年男性骨质疏松的发病中可能发挥重要作用。     

新疆维吾尔族人群骨代谢特点研究

目的探讨新疆维吾尔族人的骨代谢特点。方法收集新疆库车地区维吾尔族人血清399例,分别按性别、年龄进行分组,比较各组血清25-羟基维生素D含量。另外,抽取60例50岁以下维吾尔族女性进行骨代谢指标测定,包括钙、磷、骨钙素及雌二醇。结果维吾尔族各年龄段女性血清25-羟基维生素D含量均低于同年龄段男性(P值均小于0.05)。男性及女性的血清25-羟基维生素D水平均与年龄呈负相关(r=-0.247,P=0.000;r=-0.181,P=0.018)。50岁以下女性血清钙含量分别与磷、骨钙素呈正相关,相关系数分别为r=0.344,P=0.007;r=0.288,P=0.026。血清钙含量与雌二醇呈负相关(r=-0.27,P=0.037)。结论年龄及性别可能是影响维吾尔族人血清维生素D含量的因素之一,维吾尔族人血清钙含量与磷、骨钙素以及雌激素有关。     

阿仑膦酸钠对甲状腺功能减患者骨密度及骨生化、代谢影响的临床研究

目的观察阿仑膦酸钠对甲状腺功能减患者骨密度及骨生化、代谢影响的影响。方法初次诊断为未绝经的甲状腺功能减退女性患者64例,按随机数字表法将其分为治疗组32例,对照组32例。对照组给予左旋甲状腺素替代治疗,治疗组在对照组治疗的基础上给予阿仑膦酸钠70 mg/周,为期12个月。测定治疗不同时间段患者,腰椎1-4(L_(1-4))、左侧股骨颈BMD及血Ca~(2+)、血P~(3+)、1,25-(OH)_2D_3、碱性磷酸酶(ALP)、血清Ⅰ型胶原羧基端吡啶并啉交联肽(ICTP)以及血清骨钙蛋白(bone gla-protein,BGP)水平的变化情况。结果治疗前两组患者的骨密度及骨生化、代谢指标比较不具有统计学意义(P0.05);治疗12个月后,治疗组患者的腰椎1-4(L_(1-4))及股骨颈BMD均显著高于治疗前及同时期对照组(P0.05);治疗后12个月后,两组患者的血ALP、ICTP及BGP均有不同程度升高,治疗组的BGP升高程度明显大于对照组;而对照组的ALP及ICTP升高程度明显大于治疗组,比较有统计学意义(P0.05)。治疗前后两组患者血Ca~(2+)、血P~(3+)、1,25-(OH)_2D_3比较无明显差异(P0.05)。结论阿仑膦酸钠可以明显提升甲状腺功能减患者骨密度,改善骨生化和代谢状态。     

Serum intact molecule of bone Gla-protein in patients with abnormal bone and calcium metabolism

A circulating level of bone Gla-protein (BGP) has been estimated one of the most promising markers for bone turnover in patients with metabolic bone diseases. Although previous bone histomorphometric studies have revealed that serum BGP levels are mainly related to osteoblastic bone formation, multiple immunoreactive forms of BGP present in uremic sera are attributed to both osteoclastic bone resorption and decreased renal metabolism itself. Chromatography and cross-reactivity tests showed that an immunoradiometric assay (IRMA) for BGP specifically recognizes intact molecules of BGP and excludes BGP fragments found in uremic sera. Serum levels of BGP determined by IRMA were found significantly higher than those determined by radioimmnoassay. Elevated serum BGP levels determined by IRMA in primary hyperparathyroidism decreased and returned within the reference range more than 1 year following successful parathyroidectomy. Intermittent oral administration of high dose of 1,25 (OH)₂D₃ enhanced elevated serum BGP levels determined by IRMA which significantly increased from the initial levels at week 4 and at week 8, afterwards gradually returning to the basal levels at week 16. In addition, similar treatment effects were observed in serum prcollagen type I c-terminal peptide (P1CP), a marker for bone matrix formation. In conclusion, the measurement of serum BGP concentration utilizing IRMA, which specifically recognizes intact whole molecules of BGP, is useful to assess bone turnover and treatment effects in metabolic bone diseases, particularly in hyperparathyroidism.     

The relationship between serum vitamin D concentrations andin vivo tetracycline labeling of osteoid in crush fracture osteoporosis

Summary Twenty of 22 consecutive British patients with crush fracture osteoporosis had transiliac bone biopsies following doublein vivo tetracycline labeling synchronized with the collection of serum for the measurement of vitamin D metabolites. A significant but direct (rather than inverse) relationship was found between 25-hydroxyvitamin D (calcidiol) levels and the fraction of cancellous surfaces covered with osteoid not taking either tetracycline label (r=0.53,P<0.02). There was no correlation with 1,25-dihydroxyvitamin D levels. No patient had frankly thickneded osteoid seams although 3 had reduced but measurable calcidiol levels. These results make it unlikely that the majority of patients with osteoporosis who have osteoid of normal thickness but reduced uptake of tetracycline have a mineralization defect secondary to vitamin D deficiency. The pathophysiological significance of unlabeled osteoid in osteoporosis requires further investigation.     

Serum bone gla protein (BGP) and other markers of bone mineral metabolism in postmenopausal osteoporosis

Summary Bone gla protein, the vitamin K-dependent protein synthesized by osteoblasts and measured in blood by radioimmunoassay, has been used as an index of the rate of bone turnover. The relationship of bone gla protein with other markers of bone mineral metabolism was determined in 31 untreated postmenopausal women with the osteoporotic syndrome. In addition to serum osteocalcin (BGP) we measured parathyroid hormone (PTH) (carboxyl and mid-molecule fragments), 25(OH)D, alkaline phosphatase, estradiol (E₂), estrone (E₁), dietary calcium intake, 24 hour urinary calcium excretion, and bone mineral density by CT scan of the lumbar vertebrae. Significant osteopenia was present on CT in untreated postmenopausal osteoporotic women (bone density in 18 out of 31 was below the critical value of 60 mg/cm³). Serum BGP correlated positively with CT scan (r+0.647,P<0.001). CT and age were negatively correlated (r−0.661,P<0.001) while CT and E₂ showed a positive correlation (r+0.554,P<0.01). Unexpectedly, BGP and age revealed a significant negative correlation (r−0.421,P<0.05). These findings suggest a state of low bone turnover in this group with untreated postmenopausal osteoporosis.     

Temporal variations in iliac trabecular bone formation in vertebral osteoporosis

Summary The histologic heterogeneity of osteoporosis relative to normal controls has attracted great interest. There has been controversy as to whether patients with high turnover osteoporosis may convert to a normal or low turnover form, and vice versa. We have studied 44 patients over 12 years by dynamic histomorphometry and⁸⁵Sr kinetics + calcium balance performed within 60 days in 20 patients (Group 1) and 75–808 days apart in the remainder (Group 2). In the first group, the histologic tissue level bone formation rate (BFR/BV or BFR/BS) was predictive of the⁸⁵Sr measurements of bone formation (r=0.66P<0.01). There was no statistically significant correlation in Group 2 and the regression coefficients were significantly different (P=0.01). Periodic regression was used to determine if seasonal changes were responsible for this loss of correlation; none was found that was of statistical significance. No systematic changes with time in bone formation were found in Group 2 during the period of observation; nor were consistent secular changes detected when the data for both groups were examined according to procedure data. In conclusion, bone formation may change with time in postmenopausal osteoporosis. Evidence that these changes are systematic was not found and this has implications for the design of treatment studies.     

Bone GLA protein in predialysis chronic renal failure. Effects of 1,25(OH)2D3 administration in a long-term follow-up

Serum bone GLA protein (BGP) was measured by radioimmunoassay in 42 patients (age, 47.5 +/- 16.6 years; serum creatinine, 4.32 +/- 1.9 mg/dl) with predialysis chronic renal failure (CRF). Nineteen patients were studied within a short period of time, while 23 were followed with repeated measurements of serum BGP, creatinine, iPTH, and alkaline phosphatase (AP) for a mean period of 17.1 +/- 8.1 months. Eleven of these patients were treated with 1,25(OH)2D3 for a mean of 16.8 +/- 6.4 months. In 23 patients at various stages of CRF, a transiliac bone biopsy was performed for histomorphometric evaluation. In the untreated patients, serum BGP was higher than normal and showed a positive correlation with creatinine levels (P less than 0.001). Serum BGP was also positively correlated with iPTH, AP, serum phosphate, active resorption surface, active osteoblastic surface, osteoid surface, and volume. During treatment with 1,25(OH)2D3, BGP, iPTH, and AP were significantly lower than in the untreated patients. The reduction in iPTH and BGP was proportional, while BGP and AP no longer correlated. Repeated measurements of BGP during the long-term follow-up showed a progressive rise in the untreated patients and a downward course of BGP levels during treatment. In conclusion, serum BGP increases progressively in CRF, rising with advancing renal damage in close correlation with iPTH, AP, and the severity of renal osteodystrophy. Treatment with 1,25(OH)2D3 causes a parallel decline in BGP and iPTH levels and dissociation between BGP and AP can be observed. Compared to AP, BGP seems to be a more reliable index of secondary hyperparathyroidism and potentially more useful in the long-term monitoring of treatment with 1,25(OH)2D3.     

Interrelationship among vitamin D metabolism, true calcium absorption, parathyroid function, and age in women: evidence of an age-related intestinal resistance to 1,25-dihydroxyvitamin D action

We studied the mechanism of impaired calcium absorption with aging in 51 healthy women whose ages ranged from 26 to 88 years. Serum concentrations of 1,25-dihydroxyvitamin D [1,25-(OH)2D, mean of four measurements per subject] increased with age by 22% (P less than 0.05) but, by split-point analysis, plateaued or decreased slightly after age 65. In a subset of 20 subjects, [3H]1,25-(OH)2D3 kinetic analysis showed that this increase with age resulted from both increased production and decreased metabolic clearance of 1,25-(OH)2D. Despite the increase in serum 1,25-(OH)2D concentration, true calcium absorption did not change with age. The expected inverse correlation between true fractional calcium absorption and dietary calcium intake, however, was easily demonstrated (r = 0.66, P less than 0.001). Serum intact parathyroid hormone (PTH) increased with age by 35% (P less than 0.02) and serum bone gla protein (BGP, osteocalcin) increased by 47% (P less than 0.001); the increases in serum PTH and serum BGP were directly correlated (r = 0.32, P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Menopausal bone loss is partially regulated by dietary intake of vitamin D

Summary Five years ago we reported results from a cross-sectional study of the effect of nutritional factors on calcium-regulating hormones and bone loss in perimenopausal women. We found an inverse correlation between serum 25-hydroxyvitamin D (25OHD) and immunoreactive parathyroid hormone (PTH), and we postulated that over time, women with lower 25OHD would lose more bone because of increased bone remodeling induced by secondary hyperparathyroidism. We have followed 38 of these women for 5 years. Twenty-two have gone through menopause and we are reporting observations on these 22 subjects. Bone mineral analysis was performed twice a year at the distal and mid-radius using single-photon absorptiometry. The slope of the bone mineral content curve was calculated by least squares. Bone loss increased within 6 months of the rise in serum follicle stimulating hormone (FSH) to >40 mIU/ml. We continued to see a negative correlation between 25OHD and PTH (r=-0.450, P=0.03). Premenopause, PTH was negatively correlated with the proximal bone mineral content (PBMC) slope (-0.604, P=0.002). The distal bone mineral content (DBMC) 5-year slope was correlated with dietary vitamin D (r=0.509, P=0.02), the higher the intake, the less negative the slope. The 5-year PBMC slope was negatively correlated with serum osteocalcin (OC) levels (r=-0.382, P=0.08). Before menopause, the change in PBMC was positively correlated with OC (r=0.450, P=0.03). Postmenopause, the correlation with DBMC slope was negative (r=-0.506, P=0.05). The results provide further evidence that with uncoupling of bone remodeling after menopause, a high turnover state is associated with greater bone loss. Bone loss accelerates early in menopause, frequently before the cessation of menses. Adequate vitamin D nutritional status preserves bone mass in perimenopausal women by reducing serum PTH concentration and PTH-dependent bone remodeling.     

Osteocalcin and bone morphometric parameters in adults without bone disease

Summary Serum bone Gla-protein (s-BGP or osteocalcin) and other serum biochemical parameters were measured in 19 subjects (8 women and 11 men, aged 20–82 years) without any bone disease. Each subject simultaneously underwent an iliac crest biopsy; tetracycline double-labeling was performed in 11 subjects, allowing correlations between s-BGP and bone histomorphometric parameters. s-BGP was significantly correlated with static bone parameters: trabecular bone volume (r=0.74;P<0.001), osteoid surfaces (r=0.69;P<0.001), osteoblastic surfaces (r=0.68;P<0.002); dynamic bone formation parameters: total labeled surfaces (r=0.72;P<0.01); and the bone formation rate (r=0.69;P<0.01). We conclude that s-BGP is a valuable marker for evaluating bone formation in healthy adult subjects.     

Bone histology in steroid-treated children with non-azotemic nephrotic syndrome

Patients with nephrotic syndrome (NS) and normal glomerular filtration rate (GFR) frequently exhibit abnormalities of calcium and vitamin D homeostasis, mainly hypocalcemia and reduced circulating vitamin D metabolites. These abnormalities have been linked to alterations of bone histology in adults with non-azotemic NS, particularly osteomalacia and excessive bone resorption. Whether similar abnormalities of bone histology occur in children and adolescents with NS, particularly in those requiring prolonged treatment with corticosteroids, remains largely unknown. Thus, bone histomorphometry and selected bone-modulating hormones were studied in eight children (aged 2–16 years) with normal GFR (range 85–169 ml/min per 1.73 m²) and NS. All patients received corticosteroids for at least 12 months prior to bone biopsy. At the time of bone biopsy, the urine protein/creatinine ratio was elevated (2.1±3.6), while the average concentrations of parathyroid hormone (36±13 pg/ml), 25-hydroxyvitamin D [25(OH) D] (22±14 ng/ml), and 1,25(OH)₂D (59±22 pg/ml) were normal. Bone histomorphometry displayed focal osteomalacia (OM) and mild increased bone resorption in most patients. The mineralization lag time, an indicator of the degree of osteomalacia, correlated with the time elapsed since the original diagnosis of NS (r=0.93, P<0.0005). Overt hyperparathyroidism was not evident, but increased eroded perimeter and elevated bone formation rate (BFR) were evident in two patients, suggesting high-turnover bone disease. The BFR was inversely correlated with the administered dose of prednisone at the time of biopsy (r=–0.78, P<0.05) and one patient exhibited low bone turnover changes. The growth velocity standard deviation score (SDS) at time of biopsy ranged from –1.6 to 3.2, resulting in a height SDS range of –1.9 to 0.6. The height SDS at time of bone biopsy correlated inversely with the dose of administered glucocorticoid (r=–0.71, P<0.05) and with the duration of the disease (r=–0.7, P=0.05). These data, albeit preliminary, demonstrate that children with NS treated with prolonged corticosteroid therapy exhibit bone histopathological changes without a concomitant impairment in GFR. While the OM appears to be related to the disease process, the alterations of bone formation and the adynamic changes are likely the result of the corticosteroid therapy. The potential consequences of these findings on adult bone mass and ultimate height deserve further studies.