Cancellous bone in the anterior part of the iliac crest

Summary Calcified tissue in the iliac crest and the adjoining ala of the ilium was investigated by scanning electron micrographs of thick, polished sections from which the marrow had been removed. Some quantitative properties of the trabeculae and of the marrow spaces were obtained from measurements on the images of the polished surfaces. Most of the cortex of the crest was porous, about 25% void, of varying thickness, intruding into the cancellous space in some regions. A structure containing about 35% by volume of bone was found at and near the anterior superior spine. Compact bone of normal appearance began as thin medial and proximal sheets below the crest, and thickened until at 20–30 mm it was substantial. The cancellous bone contained by these structures was varied. Two main zones were distinguished, whose junction ran from just below the anterior superior spine to the lower portion of the iliac fossa. In the lateral zone, adjacent to the crest, there were arch-like structures, commencing from the medial and proximal walls, and meeting, or even crossing, near the centre. The medial zone was distinguished by large marrow cavities and strongly orientated trabeculae. The relative volume of bone was similar in the two zones, falling from a maximum of 15–20% to about 5% in the regions of the anterior inferior spine and the iliac fossa. The average width of the trabeculae was significantly greater in the medial than in the lateral zone (W _b (m)0.16 mm, W_b(l)0.12 mm). Inclusions of very heavily constructed trabeculae, having average widths of about 0.35 mm, were found in both zones.     

Maintenance of cortical bone in human parathyroid hormone(1-84)-treated ovariectomized rats

The purpose of this cross-sectional study was to evaluate the effects of human parathyroid hormone(1-84) (hPTH) followed by maintenance treatment with 17beta-estradiol (E(2)), risedronate (Ris), or a reduced dose of hPTH (LowPTH) on cortical bone in the ovariectomized (ovx) rat. Eight groups of ovx and one group of intact female rats (3.5 months) were left untreated for 11 weeks. For the following 12 weeks, four groups received subcutaneous injections of hPTH (75 microg/kg per day on 3 days/week) and four groups received vehicle. Treatments were then changed to E(2) (10 microg/kg per day on 2 days/week), Ris (3 microg/kg per day on 3 days/week), LowPTH (25 microg/kg per day on 3 days/week), or vehicle. Bone tissue was collected at weeks -11 (baseline), 0 (ovx effect), 12 (hPTH effect), 24, 36, and 48 (maintenance effect). Bone mineral density (BMD) and bone mineral content (BMC) of the diaphyseal femur and total cross-sectional area (Tt.Ar), marrow area (Ma.Ar), cortical area (Ct.Ar), and periosteal and endocortical bone formation of the tibia were measured. Ovariectomy resulted in lower BMD (weeks 0-48), unaffected BMC, and greater Tt.Ar (weeks 12 and 36), Ma.Ar (week 48), and Ct.Ar (weeks 0 and 12) compared with intact rats. Endocortical and periosteal bone formation were greater in the ovx than in the intact rats up to 23 weeks postovariectomy. Treatment of ovx rats with hPTH for 12 weeks resulted in greater cortical BMD, BMC, and endocortical bone formation than in intact or ovx controls. In ovx rats pretreated with hPTH and then treated with Ris for 36 weeks, BMD and BMC were greater and Ma.Ar was smaller than in ovx controls. In ovx rats pretreated with hPTH and then treated with LowPTH, BMD, BMC, Ct.Ar, and endocortical bone formation were greater and Ma.Ar was smaller than in ovx controls. Treatment of hPTH-pretreated rats with E(2) for 36 weeks did not affect cortical BMD, BMC, and Ct.Ar, although periosteal bone formation was lower in the E(2) group compared with the ovx group. Thus, in ovariectomized rats, cortical bone gained by 12 weeks of hPTH treatment was maintained for up to 36 weeks by treatment with risedronate or low-dose hPTH, but not with 17beta-estradiol.     

Serum 1-84 and 7-84 parathyroid hormone concentrations and bone in patients with primary hyperparathyroidism

BACKGROUND AND AIMS: Parathyroid hormone (PTH) acts on bone as both anabolic and catabolic factor. It includes two fractions: 1-84 (cyclase activating PTH, CAP) which increases bone turnover and serum calcium, and 7-84 (cyclase inactivating PTH, CIP) acting the opposite way. The aim of this study was to establish whether bone mineral density (BMD) and turnover in patients' primary hyperparathyroidism (HPT) are dependent on CAP and CIP concentrations. PATIENTS/METHODS: Thirty-one patients with HPT and 29 appropriately matched controls were examined. Parameters of calcium-phosphate homeostasis and BMD were estimated. RESULTS: BMD of radius shaft was lower in patients with HPT as compared with controls, whereas BMD of spine and ultradistal radius were similar. Serum calcium, bone alkaline phosphatase, total PTH, 1-84 PTH, and 7-84 PTH were higher in HPT patients, whereas serum phosphate was lower and beta cross-laps similar. Both total PTH and CAP correlated significantly with BMD of radius shaft and serum calcium concentration, but not with other examined parameters. CONCLUSION: Total and 1-84 PTH are similarly associated with examined parameters in patients with HPT. Thus, determination of serum CAP concentration does not seem to have advantages over total PTH with regard to bone mineral density and bone turnover assessment in those patients.     

Effects of teriparatide [recombinant human parathyroid hormone (1-34)] on cortical bone in postmenopausal women with osteoporosis.

Treatment with teriparatide (rDNA origin) injection [teriparatide, recombinant human parathyroid hormone (1-34) [rhPTH(1-34)]] reduces the risk of vertebral and nonvertebral fragility fractures and increases cancellous bone mineral density in postmenopausal women with osteoporosis, but its effects on cortical bone are less well established. This cross-sectional study assessed parameters of cortical bone quality by peripheral quantitative computed tomography (pQCT) in the nondominant distal radius of 101 postmenopausal women with osteoporosis who were randomly allocated to once-daily, self-administered subcutaneous injections of placebo (n = 35) or teriparatide 20 microg (n = 38) or 40 microg (n = 28). We obtained measurements of moments of inertia, bone circumferences, bone mineral content, and bone area after a median of 18 months of treatment. The results were adjusted for age, height, and weight. Compared with placebo, patients treated with teriparatide 40 microg had significantly higher total bone mineral content, total and cortical bone areas, periosteal and endocortical circumferences, and axial and polar cross-sectional moments of inertia. Total bone mineral content, total and cortical bone areas, periosteal circumference, and polar cross-sectional moment of inertia were also significantly higher in the patients treated with teriparatide 20 microg compared with placebo. There were no differences in total bone mineral density, cortical thickness, cortical bone mineral density, or cortical bone mineral content among groups. In summary, once-daily administration of teriparatide induced beneficial changes in the structural architecture of the distal radial diaphysis consistent with increased mechanical strength without adverse effects on total bone mineral density or cortical bone mineral content.     

Effects of daily treatment with parathyroid hormone 1-84 for 16 months on density, architecture and biomechanical properties of cortical bone in adult ovariectomized rhesus monkeys

Treatment with parathyroid hormone 1-84 (PTH) or teriparatide increases osteonal remodeling and decreases bone mineral density (BMD) at cortical (Ct) bone sites but may also increase bone size. Decreases in BMD and increases in size exert opposing effects on bone strength. In adult ovariectomized (OVX) rhesus monkeys, we assessed the effects of daily PTH treatment (5, 10 or 25 microg/kg) for 16 months on BMD at the radial, tibial and femoral diaphyses, and on biomechanical properties (3-point bending) of radial cortical bone and the femoral diaphysis. PTH treatment did not affect areal BMD measured by dual-energy X-ray absorptiometry at the tibial diaphysis but caused a rapid, dose-related decrease at the distal radial diaphysis. Peripheral quantitative computed tomography at the radial and femoral diaphyses confirmed a significant PTH dose-related decrease in volumetric Ct.BMD caused primarily by increased cortical area. Significant increases in cortical thickness were the result of nonsignificant increases in periosteal length and decreases in endocortical length. Histomorphometry revealed increased endocortical bone formation at the tibial diaphysis and rib, higher Haversian remodeling at the rib and increased cortical porosity at the rib and tibia. Biomechanical testing at the femoral diaphysis showed that PTH treatment had no effect on peak load, but significantly decreased stiffness and increased work-to-failure (the energy required to break the bone). Similar changes occurred in radial cortical beams but only stiffness was changed significantly. Thus, PTH treatment of OVX rhesus monkeys decreased BMD and stiffness of cortical bone but did not affect peak load, likely because of increased bone size. However, PTH treatment increased the energy required to break the femur making it more resistant to fracture.     

骨质疏松症大鼠注射重组人甲状旁腺素药动学研究

目的：研究注射用重组人甲状旁腺素rhPTH （1-84）在去卵巢骨质疏松症大鼠的药代动力学特征。方法48只大鼠（250±10）g,分成对照组（切除卵巢周围小块脂肪组织）和模型组（双侧卵巢切除）,每组8只,手术4周后皮下注射1.0、2.0、4.0 ug/kg rhPTH（1-84）,采用放射免疫分析法测定rhPTH（1-84）不同时间点的血药浓度,计算药代动力学参数。结果 rhPTH （1-84）在24～1850 pg/mL范围内线性关系良好,最低检测量为10 pg/mL;血浆提取回收率80.2％～90.6％;模型组低、中、高三个剂量的药动力学参数AUC（0-∞）分别为（24628.9±1281）、（47059.3±3311）和（96652.1±2174） ng/（ L· min）;对照组AUC（0-∞）分别为（21974.0±1587）、（42651.2±1336）和（87736.8±1938）ng/（L· min）。结论单次皮下注射rhPTH（1-84）在低、中、高3个剂量内,Cmax、AUC（0-∞）在2组动物中均呈线性代谢特征,模型组双峰特征明显,可以为设计和优化临床研究及给药方案提供重要信息。     

Parathyroid hormone 7-84 induces hypocalcemia and inhibits the parathyroid hormone 1-84 secretory response to hypocalcemia in rats with intact parathyroid glands

Biologic effects of large C-terminal parathyroid hormone (PTH) fragments, opposite to those of N-terminal PTH, have been demonstrated. C-terminal PTH fragments are co-secreted with N-terminal PTH from the parathyroids. The aim of our study was to examine whether C-terminal PTH 7-84 regulates secretion of PTH 1-84 and affects the expression of genes of relevance for parathyroid function, PTH, calcium-sensing receptor (CaR), PTH type 1 receptor (PTHR1), and PTH-related peptide (PTHrP) genes in rat parathyroid glands. PTH 7-84 induced a significant decrease in plasma Ca2+ in rats with intact parathyroid glands. Despite the reduction of plasma Ca2+, no stimulation of PTH 1-84 secretion took place. Furthermore, the PTH 1-84 secretory response to EGTA-induced acute and severe hypocalcemia was significantly inhibited by PTH 7-84. During recovery from hypocalcemia, plasma Ca2+ levels were significantly lower in the PTH 7-84-treated group, as compared with the vehicle group, and at the same time plasma PTH 1-84 levels were significantly suppressed. The expression of PTH, CaR, PTHR1, and PTHrP genes in the rat parathyroid glands was not affected by PTH 7-84. The peripheral metabolism of PTH 1-84 was not affected by PTH 7-84. PTH 7-84 did not cross-react with the rat bioactive PTH 1-84 assay. In normal rats with intact parathyroid glands, PTH 7-84 inhibited the PTH 1-84 secretory response to hypocalcemia and induced a significant decrease in plasma Ca2+. These effects of PTH 7-84 on PTH 1-84 secretion and on plasma Ca2+ levels were not associated with significant changes in PTH, PTHR1, CaR, and PTHrP gene expressions in the rat parathyroid glands. It is hypothesized that PTH 7-84 regulates PTH secretion via an autocrine/paracrine regulatory mechanism.     

Intratrabecular tunneling increases trabecular number throughout the skeleton of ovariectomized rhesus monkeys treated with parathyroid hormone 1-84

Daily treatment of ovariectomized (OVX) adult rhesus monkeys with human parathyroid hormone (PTH) 1-84 for 16 months increases trabecular bone volume (BV/TV), number (Tb.N) and connectivity at lumbar vertebra-3 (L3) and thoracic vertebra-10. We proposed that the increased Tb.N and connectivity was achieved by stimulation of intratrabecular tunneling. Using histomorphometry to determine frequency of events, we have now quantified intratrabecular tunneling at L3 and extended it to investigate the effects of PTH(1-84) treatment on trabecular bone at the proximal femur, distal radius and iliac crest of these animals. At L3, tunneling frequency was low in control sham and OVX animals ( approximately 0.05/mm(2)) but increased significantly in PTH(1-84)-treated animals (0.27, 0.49 and 0.95/mm(2) with the 5, 10 and 25 microg/kg doses, respectively). Very similar tunneling frequencies were observed at all skeletal sites in all groups. Iliac crest biopsies were also collected at baseline and after 6 months of treatment and showed significant time- and dose-related increases in tunnels. Although the pattern and magnitude of response varied slightly from site to site, PTH(1-84) treatment significantly increased Tb.N, as well as BV/TV and bone formation rate at all skeletal sites. A modest but statistically significant increase in trabecular thickness occurred only at the iliac crest. In summary, intratrabecular tunneling is rare in control monkeys, but increased substantially with PTH(1-84) treatment. This phenomenon provides a plausible explanation for the PTH(1-84)-induced increase in Tb.N observed in OVX monkeys. Moreover, these analyses allowed a comparison of the effects PTH(1-84) treatment on trabecular bone at multiple locations.     

The relationship between vitamin D and parathyroid hormone: calcium homeostasis, bone turnover, and bone mineral density in postmenopausal women with established osteoporosis

It is evident from several studies that not all patients with hypovitaminosis D develop secondary hyperparathyroidism. What this means for bone biochemistry and bone mineral density (BMD) remains unclear. The aim of this study was to investigate the effects of hypovitaminosis D (defined as a 25OHD < or = 30 nmol/l) and patients with a blunted PTH response (defined arbitrarily as a PTH within the standard laboratory reference range in the presence of a 25OHD < or = 30 nmol/l) in comparison to patients with hypovitaminosis D and secondary hyperparathyroidism (defined arbitrarily as a PTH above the standard laboratory reference range in the presence of a 25OHD < or = 30 nmol/l) and vitamin D-replete subjects (25OHD > 30 nmol/l). Four hundred twenty-one postmenopausal women (mean age: 71.2 years) with established vertebral osteoporosis were evaluated by assessing mean serum calcium, 25OHD, 1,25(OH)2D, bone turnover markers, and BMD. The prevalence of hypovitaminosis D was 39%. Secondary hyperparathyroidism was found in only one-third of these patients who maintained calcium homeostasis at the expense of increased bone turnover relative to the vitamin D-replete subjects (bone ALP mean difference: 43.9 IU/l [95% CI: 24.8, 59.1], osteocalcin: 1.3 ng/ml [95% CI: 1.1, 2.5], free deoxypyridinoline mean difference: 2.6 nmol/nmol creatinine [95% CI: 2.5, 4.8]) and bone loss (total hip BMD mean difference: 0.11 g/cm2 [95% CI: 0.09, 0.12]). Patients with hypovitaminosis D and a blunted PTH response were characterized by a lower serum calcium (mean difference: 0.07 mmol/l [95% CI: 0.08, 0.2]), a reduction in bone turnover (bone ALP mean difference: 42.4 IU/l [95% CI: 27.8, 61.9], osteocalcin: 1.6 ng/ml [95% CI: 0.3, 3.1], free-deoxypyridinoline mean difference: 3.0 nmol/nmol creatinine [95% CI: 1.9, 5.9]), but protection in bone density (total hip BMD mean difference: 0.10 g/cm2, [95% CI: 0.08, 0.11]) as compared to those with hypovitaminosis D and secondary hyperparathyroidism. This study identifies a distinct group of patients with hypovitaminosis D and a blunted PTH response who show a disruption in calcium homeostasis but protected against PTH-mediated bone loss. This has clinical implications with respect to disease definition and may be important in deciding the optimal replacement therapy in patients with hypovitaminosis D but a blunted PTH response.     

Effects of 3- and 5-year treatment with risedronate on bone mineralization density distribution in triple biopsies of the iliac crest in postmenopausal women.

Long-term effects of risedronate on bone mineralization density distribution in triple transiliac crest biopsies of osteoporotic women were evaluated. In this double-blinded study, 3- and 5-year treatment with risedronate increased the degree and homogeneity of mineralization without producing hypermineralization. These changes at the material level of bone could contribute to risedronate's antifracture efficacy. INTRODUCTION: Risedronate, a nitrogen-containing bisphosphonate, is widely used in the treatment of osteoporosis. It reduces bone turnover, increases BMD, and decreases fracture risk. To date, there are no data available on the long-term effects of risedronate on bone mineralization density distribution (BMDD) in humans. MATERIALS AND METHODS: Osteoporotic women enrolled in the VERT-NA trial received either risedronate (5 mg/day, orally) or placebo for up to 5 years. All subjects received calcium and vitamin D supplementation if deficient at baseline. Triple iliac crest biopsies were collected from a subset of these subjects at baseline and 3 and 5 years. BMDD was measured in these biopsies using quantitative backscattered electron imaging, and the data were also compared with a normal reference group. RESULTS: At baseline, both risedronate and placebo groups had a lower degree and a greater heterogeneity of mineralization as well as an increase in low mineralized bone compared with the normal reference group. The degree of mineralization increased significantly in the risedronate as well as in the placebo group after 3- and 5-year treatment compared with baseline. However, the degree of mineralization did not exceed that of normal. Three-year treatment with risedronate significantly increased the homogeneity of mineralization and slightly decreased low mineralized bone compared with placebo. Surprisingly with 5-year risedronate treatment, heterogeneity of mineralization increased compared with 3-year treatment, which might indicate an increase in newly formed bone. CONCLUSIONS: Long-term treatment with risedronate affects the homogeneity and degree of mineralization without inducing hypermineralization of the bone matrix. These changes at the material level of the bone matrix may contribute to risedronate's antifracture efficacy in osteoporotic patients.     

椎体骨质疏松骨折患者骨转换生化标志物的临床研究

目的 探讨骨转换生化标志物对于绝经后骨质疏松椎体骨折的预测价值。方法 73例绝经后骨质疏松症患者分为骨折组及非骨折组,分别测定血清I型原胶原氨基端前肽（PINP)、I型胶原交联羧基末端肽（CTX)及骨密度并比较。结果 绝经后骨质疏松骨折组患者的骨转换生化标志物水平明显高于非骨折组,其差异有显著性;而两者骨密度的差异无显著性。结论 骨转换生化标志物可以作为预测绝经后骨质疏松骨折的重要指标。     

Alterations of the mineralization profile and osteocalcin concentrations in osteoarthritic cortical iliac crest bone

Summary The relation between bone mineralization and osteocalcin content was investigated in iliac crest cortical bone obtained at necropsy in young females and in two groups of elderly women with and without osteoarthritis of the hands evaluated by X-ray. Using density fractionation technique, the bone was separated into fractions of increasing density from 1.72 to 2.30 g/ml. The mineralization profile revealed a significant shift to higher densities in the osteoarthritis cases compared with young adults (P<0.005) and age-sexmatched controls (P<0.001). The ash, calcium, and phosphorus content of the bone increased with increasing density of the fractions whereas collagen content, measured as hydroxyproline, decreased. The osteocalcin concentration of each fraction was determined in the supernatants obtained after EDTA-extraction in the presence of protease inhibitors. In the young control and osteoarthritis group, the osteocalcin content in the lowest density fractions was higher compared with the older non-osteoarthritic group. Osteocalcin content of the high density fractions, representing highly mineralized osteons, was the same in the three groups studied. These findings support the hypothesis that quality differences in bone may explain the inverse relationship between osteoarthritis and osteoporosis.     

Estrogen-dependent increase in bone turnover and bone loss in postmenopausal women with breast cancer treated with anastrozole. Prevention with bisphosphonates

Aromatase inhibitors have demonstrated their superiority to tamoxifen as adjuvant therapy for early breast cancer in postmenopausal women, but are associated with an increased risk of fractures. The aim of our study was to analyze bone loss, bone turnover and their determinants in postmenopausal women treated with anastrozole. We investigated bone loss and bone turnover markers (BTM) in a prospective open cohort study of 118 postmenopausal women treated with anastrozole for an early hormone-dependent breast cancer. Women without osteoporosis were not treated and compared with an age-matched control group of 114 healthy women. Osteoporotic patients (T-scoreor=6 courses) and a marked antiestrogenic response--defined by a level of 17beta-estradiol50% between baseline and 1 year--were associated with greater bone loss. In multivariate model, women in the highest quartile of bone loss at the spine (>5.6% at 1 year) and hip (>4.9%) had a marked antiestrogenic response with OR of 10.4 [95% C.I. 1.9-57.2] (p=0.007) and 5.7 [1.3-25] (p=0.024) respectively. Among patients in the surveillance group, those with a normal T-score at both sites (n=46) had also a significant bone loss at spine -3.3+/-0.5% [-4.3 to -2.3], p<0.0001 and at the hip -2.9+/-0.6% [-4.1 to -1.7] p<0.0001. In osteoporotic women treated simultaneously with anastrozole and risedronate, bone loss was prevented at hip, and increased at the spine (+4.1+/-0.9% [2.3 to 5.9], p=0.008), and BTM decreased (-24%, -39% for CTX, p=0.003 and 0.001 vs. changes in the untreated group). Anastrozole increases bone turnover and induces an accelerated bone loss that is significantly related to the suppression of 17beta-estradiol production induced by aromatase inhibitor. The bisphosphonate risedronate prevents anastrozole induced bone loss.     

Continuous parathyroid hormone induces cortical porosity in the rat: effects on bone turnover and mechanical properties.

We examined the time course effects of continuous PTH on cortical bone and mechanical properties. PTH increased cortical bone turnover and induced intracortical porosity with no deleterious effect on bone strength. Withdrawal of PTH increased maximum torque to failure and stiffness with no change in energy absorbed. INTRODUCTION: The skeletal response of cortical bone to parathyroid hormone (PTH) is complex and species dependent. Intermittent administration of PTH to rats increases periosteal and endocortical bone formation but has no known effects on intracortical bone turnover. The effects of continuous PTH on cortical bone are not clearly established. MATERIALS AND METHODS: Eighty-four 6-month-old female Sprague-Dawley rats were divided into three control, six PTH, and two PTH withdrawal (WD) groups. They were subcutaneously implanted with osmotic pumps loaded with vehicle or 40 microg/kg BW/day human PTH(1-34) for 1, 3, 5, 7, 14, and 28 days. After 7 days, PTH was withdrawn from two groups of animals for 7 (7d-PTH/7d-WD) and 21 days (7d-PTH/21d-WD). Histomorphometry was performed on periosteal and endocortical surfaces of the tibial diaphysis in all groups. microCT of tibias and mechanical testing by torsion of femora were performed on 28d-PTH and 7d-PTH/21d-WD animals. RESULTS AND CONCLUSIONS: Continuous PTH increased periosteal and endocortical bone formation, endocortical osteoclast perimeter, and cortical porosity in a time-dependent manner, but did not change the mechanical properties of the femur, possibly because of addition of new bone onto periosteal and endocortical surfaces. Additionally, withdrawal of PTH restored normal cortical porosity and increased maximum torque to failure and stiffness. We conclude that continuous administration of PTH increased cortical porosity in rats without having a detrimental effect on bone mechanical properties.     

The effect of an oral calcium load on plasma ionized calcium and parathyroid hormone concentrations in osteoporotic postmenopausal women

Summary Plasma ionized calcium (IC) and parathyroid hormone (PTH) concentrations were measured in 31 osteoporotic postmenopausal women at hourly intervals for 5 hours after a 1 g oral calcium load. Fifteen subjects had normal radiocalcium absorption and 16 subjects were malabsorbers of calcium. IC rose and PTH fell after the calcium load in both groups with a plateau at 3–4 hours, and the rise in IC was greater (P<0.01) in the normal absorbers. There was a nonsignificant trend for the fall in PTH to be greater in the normal absorbers. In the group as a whole the mean increase in IC (above baseline) at 4 hours was directly related to calcium absorption (P<0.025) and the mean change in PTH was inversely related to calcium absorption (P<0.05). These results demonstrate that in subjects with postmenopausal osteoporosis the responses of IC and PTH to an oral calcium load are a function of calcium absorptive status.     

Suppressed bone turnover was associated with increased osteoporotic fracture risks in non-obese postmenopausal Chinese women with type 2 diabetes mellitus

Summary

We found that type 2 diabetes mellitus (T2DM) was associated with increased fracture risks in non-obese postmenopausal Chinese women, and suppressed bone turnover might be the underlying mechanism. This is the first study evaluating and explaining the association of T2DM with osteoporotic fracture in Chinese population with such high homogeneity.

Introduction

The aim of this study was to investigate the association of T2DM with osteoporotic fracture in postmenopausal Chinese women.

Methods

One thousand four hundred ten postmenopausal women were included and stratified into non-obese population [body mass index (BMI)?<?25 kg/m²] and obese population (BMI?≥?25 kg/m²). Each type of population was classified into diabetes group, impaired fasting glucose (IFG) group, and normal glucose group. Bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry. Serum C-terminal telopeptide of type I collagen (β-CTX) and serum N-amino terminal prepeptide of type 1 procollagen (P1NP) were quantified. Vertebral fractures (VFs) and non-VFs were assessed by vertebral X-ray and questionnaire, respectively.

Results

Comparing to normal glucose group, diabetes group and IFG group both had lower levels of P1NP and β-CTX, despite population types. Despite having non-decreased BMD, non-obese diabetic patients had higher risks of total fracture and VF than BMI-matched normal glucose subjects (both P?<?0.05). Non-obese population was further classified by a mean value of P1NP or β-CTX. Non-obese diabetic patients with low P1NP or high β-CTX had higher fracture risks (both P?<?0.05), comparing to non-obese normal glucose subjects with high P1NP or high β-CTX, respectively.

Conclusions

Type 2 diabetic patients had suppressed bone turnover, which might explain the increased fracture risks, independent of BMD. IFG patients might also have poor bone quality and need early prevention.     

Growth hormone treatment in adults with adult-onset growth hormone deficiency increases iliac crest trabecular bone turnover: a 1-year, double-blind, randomized, placebo-controlled study.

The effects of growth hormone (GH) substitution on bone metabolism were evaluated by dynamic histomorphometry on iliac crest bone biopsies. Twenty-nine patients, aged 21-61 years (mean 45.5 years), with adult-onset GH deficiency (GHD) were randomized to receive subcutaneous injections with GH (2 IU/m2/day = 0.67 mg/m2/day) or placebo for 12 months. Serum insulin-like growth factor I (IGF-I) levels increased 263 +/- 98% (mean +/- SD) during GH treatment (p < 0.0001). In the GH group, osteoid surface increased during treatment from 11% (3-15%) (median [25-75 percentiles]) to 21% (10-27%) (p = 0.01) and mineralizing surface from 4% (1-8%) to 11%(7-16%) (p = 0.04). Moreover, erosion surface tended to increase in the GH group from 2% (1-3%) to 4% (3-5%) (p = 0.07). The quiescent surface decreased in the GH group from 87% (83-96%) to 74% (68-87%) (p = 0.01). The adjusted appositional rate, mineral apposition rate, bone formation rate, bone erosion rate, mineralization lag time, and osteoid thickness remained unchanged during treatment. Erosion depth showed a trend toward increase in the GH group (p = 0.09), whereas wall thickness was unchanged. Bone balance at the remodeling unit level and activation frequency were unchanged. At the tissue level, bone erosion rate increased significantly from 26% (17-36%)/year to 39% (23-72%)/year (p = 0.03). Similarly, the bone formation rate at the tissue level tended to increase, from 24% (15-31%)/year to 36% (17%-63%)%/year (p = 0.06). Finally, bone balance at the tissue level decreased significantly from 1% (-2-2%)/year to -5% (-13-1%)/year (p = 0.01). No significant difference in change was seen in the cancellous bone volume. We conclude that 12 months of GH substitution therapy increases trabecular bone turnover. Moreover, our data suggest that bone balance at the bone multicellular unit level is not changed to positive.     

Daily parathyroid hormone 1-34 replacement therapy for hypoparathyroidism induces marked changes in bone turnover and structure

Parathyroid hormone (PTH) has variable actions on bone. Chronically increased PTH is catabolic and leads to osteoporosis; yet intermittent administration is anabolic and increases bone mass. PTH deficiency is associated with decreased bone remodeling and increased bone mass. However, the effects of PTH replacement therapy on bone in hypoparathyroidism are not well known. We discontinued calcitriol therapy and treated 5 hypoparathyroid subjects (2 adults and 3 adolescents) with synthetic human PTH 1‐34 (hPTH 1‐34), injected two to three times daily for 18 months, with doses individualized to maintain serum calcium at 1.9 to 2.25 mmol/L. Biochemical markers and bone mineral density (BMD) were assessed every 6 months; iliac‐crest biopsies were performed before and after 1 year of treatment. hPTH 1‐34 therapy significantly increased bone markers to supranormal levels. Histomorphometry revealed that treatment dramatically increased cancellous bone volume and trabecular number and decreased trabecular separation. Changes in trabecular width were variable, suggesting that the increase in trabecular number was due to the observed intratrabecular tunneling. Cortical width remained unchanged; however, hPTH 1‐34 treatment increased cortical porosity. Cancellous bone remodeling was also stimulated, inducing significant changes in osteoid, mineralizing surface, and bone formation rate. Similar changes were seen in endocortical and intracortical remodeling. BMD Z‐scores were unchanged at the spine and femoral neck. Total hip Z‐scores increased; however, total body BMD Z‐scores decreased during the first 6 months of treatment and then stabilized, remaining significantly decreased compared to baseline. Radial Z‐scores also decreased with treatment; this was most pronounced in the growing adolescent. Daily hPTH 1‐34 therapy for hypoparathyroidism stimulated bone turnover, increased bone volume, and altered bone structure in the iliac crest. These findings suggest that treatment with hPTH 1‐34 in hypoparathyroid adults and adolescents has varying effects in the different skeletal compartments, leading to an increase in trabecular bone and an apparent trabecularization of cortical bone. Published 2012 American Society for Bone and Mineral Research. This article is a US Government work and, as such, is in the public domain in the United States of America.