Biochemical Markers of Bone Turnover Reflect Femoral Bone Loss in Elderly Women

Although over 90% of hip fractures occur in patients over age 70, few data are available on femoral bone loss in this age group. To examine the relationship between biochemical markers of bone turnover and femoral bone loss in the elderly, 36 female and 17 male, healthy, community-dwelling elderly over age 65 (mean ± SD age: women 71 ± 4 years, men 75 ± 5 years) were followed for 3 years. Annual bone mineral density measurements of the hip and lumbar spine by dual-energy x-ray absorptiometry (DXA) were obtained and biochemical markers of bone resorption (urinary N-telopeptide crosslinks, free pyridinoline, total pyridinoline, total deoxypyridinoline, and hydroxyproline) and bone formation (serum osteocalcin, bone-specific alkaline phosphatase) were obtained at the end of year 3. In elderly women, longitudinal bone loss at the total hip was negatively correlated with markers of bone resorption (r =−0.39 to −0.52, P < 0.05), bone formation (r =−0.38, P < 0.05), and age (r =−0.39, P < 0.05). Markers of bone resorption were correlated with markers of bone formation (r = 0.63 to 0.74, P < 0.01). In multiple regression analysis, urinary N-telopeptide crosslinks (marker of resorption), serum osteocalcin (marker of formation), and serum parathyroid hormone explained 43% of the variability of bone loss at the total hip in women. These parameters were not related to bone loss in men. We conclude that femoral bone loss increases with age in women over 65. Measurements of specific biochemical markers of bone turnover are correlated with longitudinal bone loss in elderly women. These markers may help identify women at greatest risk for bone loss who would benefit most from therapeutic interventions. Received: 28 January 1996 / Accepted: 3 May 1996     

Calcaneal Ultrasound but Not Bone Turnover Predicts Fractures in Vitamin D Deficient Frail Elderly at High Risk of Falls

Background Biochemical markers of bone turnover have been reported to predict fracture risk independent of bone mass in postmenopausal women. We investigated their use in predicting fractures in the frail elderly. Methods Cases were 151 low trauma fractures. For each case, a control was selected marched for sex, age, institution type and follow-up period. We measured two bone resorption markers (serum ICTP and serum CTX-I) and two bone formation markers (serum PINP and serum BAP). Quantitative Ultrasound (QUS) was measured in the calcaneus. Fractures were ascertained by x-ray reports. Results The mean age of subjects was 86.8 years (± 5.8 SD) and 86% were female. 76% had hypovitaminosis D (a serum 25 hydroxy vitamin D (25OHD) level < 39 nmol/L) and 81% had BUA < 67.4 dB/MHz (corresponding to a BMD T-score < −2.5). No significant differences in bone turnover markers were detected between fracture cases and their matched controls. In contrast, there was a significant difference between cases and controls for both broadband ultrasound attenuation (BUA) and velocity of sound (VOS) (both P < 0.05). These results remained the same after adjusting for weight, lower leg length and walking aids as well as the higher falls incidence in cases than controls (average 2.7 vs 0.9 falls respectively; P < 0.001) during the follow-up period. Conclusion In the frail elderly with vitamin D deficiency and high falls risk, calcaneal ultrasound but not markers of bone turnover were associated with fractures.     

Change of cross-linked telopeptide of type I collagen (ICTP) and other bone resorption markers in patients with bone fragility fractures

Background The serum concentration of cross-linked telopeptide of type I collagen (ICTP) has been reported to be a useful marker and for both diagnosis and monitoring of bone metastasis. This study was performed to clarify the changes in various bone turnover markers, including ICTP, after bone fragility fracture. Methods Seventy-six bone fragility fracture patients (14 men and 62 postmenopausal women; mean age, 77.0 years) were evaluated for bone resorption markers, including serum ICTP. We measured urinary N-terminal telopeptides of type I collagen (NTX) several times after fracture. Furthermore, serum ICTP, serum NTX, urinary deoxypyridinoline (DPD), and urinary C-telopeptide-cross-linked type I collagen (CTX) were measured at the times of both minimum and maximum urinary NTX. Results Urinary NTX was increased significantly from 86.4 ± 57.9 to 214.3 ± 137.2 nmol BCE/mmol Cr following fracture. Serum ICTP showed a similar significant increase from 7.6 ± 4.7 to 10.4 ± 5.5 ng/ml in bone fragility fracture patients. Furthermore, other markers also showed similar increases. The level of increase in urinary NTX (148.0%) was especially high compared with other bone resorption markers. On the other hand, the level of increase in serum ICTP (36.8%) was similar to that in serum NTX (39.8%). Serum ICTP levels were significantly correlated with other bone resorption markers, with an especially strong correlation between serum ICTP and serum NTX (r = 0.647, P < 0.001). The percentage of cases in which ICTP exceeded the cutoff value for suspected bone metastasis in postmenopausal women was 73.6%. Conclusions The value of ICTP increases with bone fragility fracture and is correlated with other bone resorption markers, and ICTP obviously exceeded the reference value as compared with other bone resorption markers.     

Effect of intranasal salmon calcitonin therapy on bone mass and bone turnover in early postmenopausal women: A dose-response study

We examine the dose-related effect of intranasal salmon calcitonin (sCT) on the early postmenopausal bone loss and bone turnover; a 2-year, prospective, randomized, double-blind, placebo-controlled study was carried out with 134 healthy women who had passed a natural menopause within 6 months to 3 years. The women were allocated randomly to 2 years of treatment with either 100, 200, or 400 IU of sCT given intranasally or placebo. All groups received a calcium supplement of 500 mg. Twenty-one women left the study before its end and 91 complied with the study criteria throughout. Bone mineral content/density of the distal forearm and lumbar spine and biochemical parameters of bone turnover were measured. Although the measurements after 24 months revealed no significant difference between groups in bone mineral density of the lumbar spine, the average changes over time revealed prevention of bone loss in the groups treated with 200 and 400 IU of sCT (0.2 to-0.6%) and declines of 0.8-1.7% in the groups treated with 100 IU of sCT and placebo (P<0.05–0.01; within-group testing). There was no dose-related response to sCT but there was a significant difference between the pooled groups treated with 200 plus 400 IU of sCT versus the 100 IU sCT and placebo-treated groups (P=0.030–0.005). The same difference between groups was seen for biochemical parameters of bone turnover (P=0.022–0.003). The biochemical parameters of bone turnover revealed decreases of 10–20% (P<0.001; within group testing) in the groups treated with the two highest sCT doses. It was concluded that nasal sCT in doses of 200 and 400 IU has some effect in women soon after the menopause—preventing the bone loss in the spine throughout the first year of therapy and lowering the bone turnover. It may be used as an alternative to hormone replacement when estrogens are contraindicated. The present data indicate that discontinuous strategies should be preferred.     

The role of serum concentrations of sex steroids and bone turnover in the development and occurrence of postmenopausal osteoporosis

Summary It has been debated whether postmenopausal osteoporosis is characterized by high or low bone turnover and whether circulating levels of sex steroids contribute to the occurrence of osteoporotic fractures. We examined 154 70-year-old women with or without osteoporotic fractures, and 178 early postmenopausal women with a “rapid” or a “slow” bone loss. In all participants, we determined markers of bone formation (serum alkaline phosphatase (AP) and serum bone Gla protein (BGP)), markers of bone resorption (fasting urinary calcium/creatinine (FU Ca/Cr) and hydroxyproline/creatinine (FU Hpr/Cr)), and serum estrone (E₁), estradiol (E₂), androstenedione (A), and fat mass. The 70-year-old womenwith osteoporotic fractures had significantly elevated AP (P<0.001), BGP (P<0.001), and FU Hpr/Cr (P<0.001) compared with the groupwithout fractures. In the group of early postmenopausal women, the “rapid” bone losers had significantly increased FU Hpr/Cr (P<0.001) and FU Ca/Cr (P<0.001). E₁, E₂, A, and the fat mass did not differ in the groups with and without osteoporotic fractures, whereas the “rapid” bone losers had significantly lower E₁ (P<0.05), E₂ (P<0.05), and fat mass (P<0.01) than the ‘slow” bone losers. It is concluded that patients with manifest osteoporosis and early postmenopausal women with a rapid bone loss have increased biochemical markers of bone turnover. Moreover, the present study demonstrates that early postmenopausal women with an “excessive” bone loss have significantly decreased serum estrogens, whereas it is not possible to detect low estrogens in women with osteoporotic fractures.     

Effects of 8 Years of Treatment with Tibolone 2.5 mg Daily on Postmenopausal Bone Loss

The objective of this study was to assess the long-term effects of tibolone 2.5 mg daily (Livial¹; Organon) on bone mineral density in recently postmenopausal women. An 8-year, open, nonrandomized, prospective study was designed to compare the effects of tibolone 2.5 mg daily (n= 59) with an untreated control group (n= 51). The subjects of this study were 110 recently postmenopausal women (6–36 months since last menstrual period). The main outcome measures were bone mineral density of the spine and femur, measured by dual-energy X-ray absorptiometry, and assessment of biochemical markers of bone metabolism. After 8 years of tibolone use, the mean (± SEM) increase in bone mineral density compared with baseline was 4.1%± 0.8% (p<0.0001) in the spine and 4.6%± 1.8% (p= 0.015) in the femoral neck. Over the same period, bone mineral density in the control group decreased in the spine by –7.5%± 1.1%, (p<0.0001) and in the femur by –6.7%± 1.2% (p<0.0001). The bone resorption marker, calcium/creatinine ratio, decreased in the tibolone group but not in the control group. Serum bone formation markers decreased (alkaline phosphatase) or stayed approximately the same (osteocalcin) in the tibolone group. Adherence was high, with 58% (34 of 59) of the tibolone group continuing treatment for 8 years. We conclude that tibolone 2.5 mg daily prevents bone loss in the lumbar spine and femoral neck over 8 years and adherence to treatment is high. The greater bone density compared with untreated women would be expected to reduce the risk of bone fractures. Received: September 2000 / Accepted: December 2000     

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.     

An effective regimen of intranasal salmon calcitonin in early postmenopausal bone loss

Summary In order to devise a convenient and effective therapeutic regimen of intranasal salmon calcitonin (sCT) for the treatment of early postmenopausal bone loss, we studied the effects of a 1-year course of sCT nasal spray on vertebral mineral content (VMC), assessed by dual photon densitometry, and bone turnover in 21 early postmenopausal osteoporotic women. Subjects enrolled in the study had a value above the normal average of at least one index of bone turnover: whole body retention (WBR) of ^99mTc-methylenedichloro-bisphosphonate (^99mTc-MDP), serum bone gla protein (BGP), urinary hydroxyproline/creatinine excretion (HOP/Cr). After baseline evaluation, patients were randomized for treatment with either sCT (200 IU every other day) or plabebo. Treatment with sCT significantly increased VMC by 2.7±0.9% at 6 months, and 3.3±0.8% at 1 year, whereas a progressive decline was observed in the placebo group (-2.6±0.5%, and -3.5±0.5% after 6 and 12 months, respectively). These changes were associated with a progressive and significant reduction of all parameters of bone turnover in the sCT-treated patients, whereas no changes were detected in the control group during the study period. The differences between the two groups were significant after 1 year for VMC, BGP, and WBR (P<0.05, one-way analysis of variance). Thus, 200 IU intranasal sCT administered on alternate days is adequate to stop the fast bone loss occurring early after the menopause in women with high bone turnover rates. This therapeutical modality represents an important addition to the available pharmacologic spectrum for the prevention and treatment of postmenopausal osteoporosis.     

Suppression of Bone Resorption in Early Postmenopausal Women by Intranasal Salmon Calcitonin in Relation to Dosage and Basal Bone Turnover

In the present study, we assessed the ability of increasing doses of intranasal calcitonin to suppress urinary deoxypyridinoline cross-link (DPD), a specific biochemical marker of bone resorption, in early postmenopausal women. Subjects consisted of 30 healthy Thai women within 5 years of postmenopause, randomly assigned to 50, 100, or 200 IU of intranasal calcitonin 5 days/week for 3 months. Calcium supplementation by calcium carbonate capsules at 750 mg of elemental calcium per day was given to all subjects. Twenty four-hour urine for DPD and creatinine assays was collected at baseline, 1 month, and 3 months after treatment. All DPD values were corrected with urinary creatinine before analyses. Data were expressed as mean ± SEM. DPD decreased significantly 1 month after intranasal calcitonin treatment (P < 0.01). However, at 3 months, DPD increased when compared with the values at 1 month (P < 0.01), suggesting that there may be a reduction in the suppression of bone resorption after prolonged calcitonin therapy. Using a stepwise multiple regression model to address whether dosage and DPD at baseline influence the response to intranasal calcitonin, it was found that DPD suppression after intranasal calcitonin was not related to dosage but was strongly associated with baseline DPD (P < 0.0001). Suppression of bone resorption in early postmenopausal women by intranasal calcitonin is determined more by the state of bone turnover at baseline than the dosage of calcitonin. Received: 10 March 1997 / Accepted: 14 November 1997     

Longitudinal Assessment of In Vivo Bone Dynamics in a Mouse Tail Model of Postmenopausal Osteoporosis

Recently, it has been shown that transient bone biology can be observed in vivo using time-lapse micro-computed tomography (μCT) in the mouse tail bone. Nevertheless, in order for the mouse tail bone to be a model for human disease, the hallmarks of any disease must be mimicked. The aim of this study was to investigate whether postmenopausal osteoporosis could be modeled in caudal vertebrae of C57Bl/6 mice, considering static and dynamic bone morphometry as well as mechanical properties, and to describe temporal changes in bone remodeling rates. Twenty C57Bl/6 mice were ovariectomized (OVX, n = 11) or sham-operated (SHM, n = 9) and monitored with in vivo μCT on the day of surgery and every 2 weeks after, up to 12 weeks. There was a significant decrease in bone volume fraction for OVX (−35%) compared to SHM (+16%) in trabecular bone (P < 0.001). For OVX, high-turnover bone loss was observed, with the bone resorption rate exceeding the bone formation rate (P < 0.001). Furthermore there was a significant decrease in whole-bone stiffness for OVX (−16%) compared to SHM (+11%, P < 0.001). From these results we conclude that the mouse tail vertebra mimics postmenopausal bone loss with respect to these parameters and therefore might be a suitable model for postmenopausal osteoporosis. When evaluating temporal changes in remodeling rates, we found that OVX caused an immediate increase in bone resorption rate (P < 0.001) and a delayed increase in bone formation rate (P < 0.001). Monitoring transient bone biology is a promising method for future research.     

Comparison of Three Bone Densitometry Methods in Osteoporotic Women

Three techniques of bone mass measurement were evaluated in the diagnosis of postmenopausal osteoporosis; the overlap in the measurements and the capacity for discriminating was determined among 51 postmenopausal normal (mean age 66.6 ± 8.4 years) and 42 postmenopausal osteoporotic women (mean age 68.5 ± 7.5 years). All bone mass was evaluated by total body bone mineral content (BMC_TB), density (BMD_TB), ultrasound bone velocity (UBV) in proximal phalanxes 2–5 of the nondominant hand (UBV = mean value of all ultrasound measurements), and peripheral quantitative computed tomography of the nondominant forearm (pQCT). BMC_TB was found to be significantly better (P < 0.0001) for diagnosing postmenopausal osteoporosis than the other methods; both cortical and trabecular pQCT measurements were more discriminating than the corresponding UBV measurements (P < 0.001). T-score values in normals, subjects versus osteoporotic ones were BMC_TB−1.15 ± 0.79 versus −3.17 ± 0.74; BMD_TB−1.01 ± 0.97 versus −3.28 ± 0.81; UBV −1.51 ± 1.02 versus −2.34 ± 1.21; trabecular-pQCT −0.40 ± 0.72 versus −1.57 ± 0.37; cortical-pQCT −1.00 ± 0.87 versus −2.67 ± 0.53; and total-pQCT −0.65 ± 1.01 versus −2.34 ± 0.27, respectively. The overlap in values between the postmenopausal normal and postmenopausal osteoporotic groups was 50% with UBV, 6% with BMC_TB, 9% with BMD_TB, 25% with cortical pQCT, and 42% with trabecular pQCT. BMC_TB, BMD_TB, UBV, and pQCT correlated well with each other as measurements of bone mass, but BMC_TB was more discriminating than the other measurements in the diagnosis of osteoporosis. Received: 7 June 1995 / Accepted: 21 May 1997     

Assessment of the bone status of Nigerian women by ultrasound and biochemical markers

Ultrasound analysis of the calcaneus and serum markers of bone turnover were used to examine the bone status of healthy Nigerian women who reside in an area of the world where dietary calcium intake is generally low and estrogen replacement therapy is not widely available. A total of 218 women (108 premenopausal and 110 postmenopausal) between the ages of 16 and 95 years were enrolled in the study. Broadband ultrasound attenuation (BUA) and speed of sound velocity (SOS) were measured and used to calculate the stiffness index (SI) of the calcaneus. In this cross-sectional study, the Nigerian women exhibited a marked age-dependent decline in SI that was defined by the regression equation SI=105.9–6.62E-3×Age². SI was significantly correlated with age (r=−0.41,P<0.001) and with serum NTx concentrations (r=−0.26,P<0.001), but not with serum levels of bone specific alkaline phosphatase (BSAP). Years since menopause was also significantly correlated with SI (r=0.40,P<0.001). A significant increase in serum NTx concentration occurred at least a decade before a significant decline in SI was evident. In the total study group, 24% of the women had T-scores indicative of osteopenia and 9% had T-scores indicative of osteoporosis, based on US reference data. Although the reported current incidence of fracture is low in women in sub-Saharan West Africa, these data show that after menopause Nigerian women have a decline in bone quality and increase in bone turnover similar to North American Caucasian women.     

Effects of a combined alendronate and calcitriol agent (Maxmarvil®) on bone metabolism in Korean postmenopausal women: a multicenter, double-blind, randomized, placebo-controlled study

Introduction A randomized, double-blind, prospective, 24-week clinical trial was performed to evaluate the effects of a combinative agent, Maxmarvil, of calcitriol (0.5 μg) and alendronate (5 mg) on bone metabolism in postmenopausal women.Methods A total of 217 postmenopausal women with osteoporosis were enrolled; 199 patients were randomly assigned to one of two treatment groups (Maxmarvil group or alfacalcidol group). None of the patients were vitamin-D-deficient, as assessed by serum 25-hydroxyvitamin D (25(OH)D), nor had they received any drugs affecting bone metabolism before enrollment. Bone mineral densities (BMD) of L1–L4 and the femur were measured by dual-energy X-ray absorptiometry (DXA) at the initial assessment and after 6 months of treatment. Serum biochemical assays, including serum calcium, 24-h urinary calcium excretion, and bone turnover markers (both bone-specific alkaline phosphatase [bsALP] and urine N-telopeptide [NTx]), were performed at the baseline and after 3 and 6 months of treatment.Results In the Maxmarvil group, the BMD of the lumbar spine increased up to 2.42±0.5% from the baseline after 6 months (p<0.05). On the other hand, the change in BMD in the alfacalcidol group was 0.28±0.5% after 6 months. There was no significant difference in femoral BMD between the two groups. The levels of bsALP and NTx were significantly lower in the Maxmarvil group than in the alfacalcidol group (−22.04±3.9% vs. −11.42±2.8% [p<0.05] and −25.46±5.2% vs. 1.24±6.2% [p<0.001], respectively). Interestingly, there was a significantly smaller amount of 24-h urinary calcium in the Maxmarvil group (p<0.05).Conclusions Our study demonstrates that a combination of calcitriol and alendronate is quite effective in preventing bone loss, with the advantage of lesser hypercalciuric effect of calcitriol in the postmenopausal osteoporotic women.     

Circulating osteoprotegerin and receptor activator of NF-κB ligand system in patients with β-thalassemia major

Osteoporosis represents an important cause of morbidity in patients with β-thalassemia major, and its etiology is multifactorial. Thus, the aim of this study was to characterize the possible role of the osteoprotegerin (OPG) and receptor activator of the NF-κB ligand (RANKL) system in thalassemia-related bone loss. Serum concentrations of OPG, soluble RANKL (s-RANKL), markers of bone turnover, and lumbar spine bone mineral density (BMD) were measured in random samples of males (n = 29; mean age ± SEM, 24.26 ± 1.29 years; range, 13–41 years) and females (n = 31; age, 24.59 ± 0.95 years; range, 12–34 years) with β-thalassemia major and in 30 healthy age-, height-, and weight-matched subjects. Thalassemic patients had significantly lower levels of OPG compared with controls (2.54 ± 0.12 vs. 3.25 ± 0.122, respectively; P < 0.05) and higher, albeit not statistically significantly, serum levels of s-RANKL (0.350 ± 0.03 vs. 0.295 ± 0.046, respectively; P < 0.05). s-RANKL correlated negatively with age (r = −0.3, P < 0.05), and OPG correlated positively with the duration of the interval between the onset of transfusions and chelation therapy (r = 0.52, P < 0.001). Regarding markers of bone metabolism, plasma values of osteocalcin correlated positively with s-RANKL (r = 0.40, P < 0.05) and negatively with OPG/s-RANKL ratio (r = −0.55, P < 0.01). In multiple regression analysis only cross-linked N-teleopeptide of type I collagen (NTX) significantly accounted for BMD. Although the OPG/RANKL system may have some clinical usefulness as a marker of bone turnover in β-thalassemia, conventional markers of bone turnover more accurately represent changes in the BMD of these patients.     

Effect of minodronic acid hydrate on hip geometry in Japanese women with postmenopausal osteoporosis

Dual-energy X-ray absorptiometry-based hip structural analysis was performed to evaluate the effect of a bisphosphonate, minodronic acid hydrate, on the geometry of the proximal femur in Japanese patients with osteoporosis. The subjects were 103 postmenopausal patients (average age 63.9 ± 6.4 years) with primary osteoporosis. Minodronic acid hydrate was administered orally at a dose of 1 mg/day for 12 months. Significant early responses at 3–6 months after the start of administration were observed in all three regions of the proximal femur (narrow neck, intertrochanter, and shaft) in terms of bone density, geometry, and bone strength indices. The outcomes of therapy included a reduction of the internal diameter of the cortical bone (−0.1, −0.6, and −0.2% in the neck, intertrochanter, and shaft, respectively, at 12 months; not significant) and a significant increase in cortical thickness (3.1, 3.7, and 2.0% in the respective regions at 12 months). Furthermore, minodronic acid hydrate induced a significant enlargement of the cross-sectional bone area, which is related to compressive strength; a significant increase in cross-sectional moment of inertia and section modulus (SM 4.9, 5.8, and 2.9% in the neck, intertrochanter, and shaft, respectively, at 12 months; P < 0.001), which are related to the bending strength; and a significant reduction in buckling ratio (BR −3.0% (P < 0.001), −4.2% (P < 0.001), and −1.4% (P < 0.05) in the respective regions at 12 months), which reflects improved cortical stability. These findings show that minodronic acid hydrate reduces age-related endocortical bone resorption, leading to increased cortical thickness and sustained or enhanced bone strength.     

Increased Serum Levels of N-Telopeptides (NTx) of Bone Collagen in Postmenopausal Nigerian Women

Serum levels of cross-linked N-telopeptides (NTx) of bone collagen, alkaline phosphatase (ALP), and intact parathyroid hormone (PTH) were determined in 64 premenopausal (PRM) and 86 postmenopausal (PSM) women living in northern Nigeria. Serum NTx values were correlated with ALP activity (r = 0.31–0.58, P < 0.01) and PTH (0.32–0.35, P < 0.01)) in all of the subjects studied, and were also related to age (−0.47, P < 0.001) and body mass index (−0.45, P < 0.001) in PRM women. Menopause had the effect of increasing the circulating concentrations of NTx and ALP activity by 15% (P= 0.001) and 11% (P= 0.02), respectively; however, serum levels of PTH were not different between these two groups of women. Compared with Caucasian counterparts matched for age and body mass index, PSM Nigerian women had significantly increased circulating concentrations of NTx (21.7 versus 16.2 nmol BCE/liter, P= 0.01) and demonstrated a trend towards higher ALP activities and PTH levels. These results indicate that (1) discrete reference intervals should be defined for biochemical markers of bone metabolism in African populations, (2) Nigerian women have relatively higher rates of bone turnover, and (3) further investigation of the implications of increased serum NTx should be undertaken using physical methods such as dual X-ray absorptiometry (DXA) and bone ultrasound attenuation. Received: 16 September 1998 / Accepted: 10 January 1999     

A new biochemical marker of bone resorption for follow-up on treatment with nasal salmon calcitonin

In a double-blind, placebo-controlled, randomized group comparison, new and specific biochemical markers for bone resorption as follow-up parameters on the therapeutic response to nasal salmon calcitonin (sCT) were evaluated. Evaluation took place at an outpatient clinic where osteoporosis was being researched. The subjects included 208 women aged 68–72 treated for 2 years with either 50 IU, 100 IU, or 200 IU of nasal sCT or placebo; all groups received a daily calcium supplementation of 500 mg. Only 164 women fulfilled the study as valid completers. Markers were applied to frozen urine samples of a previously published intervention study of a new fasting urinary (fU) biochemical marker for bone resorption (CrossLaps^TM, ELISA) and the urinary excretion of cross-links (pyridinoline and deoxypyridinoline) was measured, all corrected for creatinine. Bone mineral density of the lumbar spine and rates of vertebral and peripheral fractures were measured after 2 years of treatment. The creatinine corrected urinary pyridinoline, deoxypyridinoline, and CrossLaps showed maximum decreases of 10–43% (95% confidence interval-29.5% to 9.6% and -75.1% to 9.3%;P < 0.01-0.001) after 6–9 months, after which the response leveled off. A significant difference among the four treatment groups was seen in fU CrossLaps(P < 0.01). The changes in spinal bone mass were significantly related to the decreases in fU CrossLaps: women with the highest response in spinal bone mass had decreases in fU CrossLaps of 44% (-83.5% to 7.4%) and women without response of 5% (-57.6% to 99.9%)P 0.001). In women who fractured during the 2-year period, fU CrossLaps remained unchanged, whereas decreases of 30% (-75.1% to 44.7%) were seen in women who did not fracture(P = 0.002). The results suggest that biochemical markers can be used to determine the optimum treatment regimen of nasal sCT. The response of the new marker, fU CrossLaps, significantly reflects the responses in bone mass of the spine and fracture rates.     

Specific Changes of Urinary Excretion of Cross-Linked N-Telopeptides of Type I Collagen in Pre- and Postmenopausal Women: Correlation with Other Markers of Bone Turnover

Urinary excretion of cross-linked N-telopeptide of type I collagen (NTx) has been reported to be a specific marker of bone resorption [18]. We assessed a new immunoassay for NTx as an indicator of changes in bone resorption caused by spontaneous menopause and compared cross-sectionally the levels of urinary NTx, hydroxylysylpyridinoline (HP), lysylpyridinoline (LP), hydroxyproline (OH-Pr), other serum biochemical indices, and lumbar spine and proximal femur bone mineral density (BMD). Eighty-one Japanese women aged 22–77 participated in this study; 36 were premenopausal and 45 were postmenopausal. Urinary HP, LP, and NTx stayed at low levels in the premenopausal period and rose 21%, 30%, and 67% in the postmenopausal period, respectively. The rise in LP and NTx was statistically significant (P < 0.01), suggesting that NTx is mostly released from bone matrix when bone resorption is accelerated. When premenopausal women were divided into two age groups and postmenopausal women were divided into two groups according to years since menopause (YSM) there were significant differences in LP and NTx between women <4 YSM and women aged <40 and those women aged 41+ (P < 0.01 and P < 0.05, respectively). A significant 110% increase in urinary NTx and a 48% increase in urinary LP were observed in postmenopausal women compared with age-matched premenopausal women aged 45–55. All biochemical markers other than serum PTH correlated significantly with each other (r = 0.243–0.858, P < 0.05–0.0001). Urinary NTx inversely correlated with lumbar spine BMD. When postmenopausal women were divided into three groups, the correlation between bone resorption and formation markers in women 0-1 YSM was greater than in women 2–10 YSM and in women 11 + YSM, indicating that resorption and formation are coupled at the early postmenopausal period. We conclude that urinary NTx is responsive to changes in bone metabolism caused by estrogen deficiency and may be a more sensitive and specific marker than HP, LP, or OH-Pr in the early postmenopausal years. Received: 15 February 1995 / Accepted: 18 October 1996     

The effects of brisk walking on markers of bone and calcium metabolism in postmenopausal women

Weight-bearing exercise has been shown to maintain or increase bone mass in younger as well as older individuals but the mechanisms by which mechanical loading affects bone metabolism are not known in detail. Twelve postmenopausal women participated in a single bout of brisk walking (50% of VO_{2 max}) for 90 minuttes. Calciotropic hormones and markers of type I collagen formation (PICP) and degradation (ICTP) were measured before the exercise, and 1, 24, and 72 hours following the exercise. Total body bone mineral content (BMC) and density (BMD) were measured by dual energy X-ray absorptiometry (DXA). Brisk walking did not induce any significant changes in the concentrations of ionized calcium, parathyroid hormone (PTH), calcitonin, or osteocalcin. A significant increase of PICP was noted 24 and 72 hours (P<0.01) after exertion and a significant decrease in the concentration of serum ICTP at 1 hour (P<0.05) was followed by an increase at 72 hours (P<0.001). There was no significant difference between the increases in the concentrations of PICP and ICTP at 72 hours. Strong inverse correlations between the basal levels of PTH and BMD (r=−0.78;P<0.01) as well as between osteocalcin and BMD (r=−0.83;P<0.01) were noticed. The changes in serum levels of bone collagen markers indicate an altered bone collagen turnover due to this moderate endurance exercise. The results also support the fact that serum levels of PTH as well as those of osteocalcin are associated with total body BMD in postmenopausal women.     

Age-related changes in bone biochemical markers and their relationship with bone mineral density in normal Chinese women

Measurements of bone biochemical markers are increasingly being used to evaluate the state of bone turnover in the management of bone metabolic diseases, especially osteoporosis. However, changes in the bone turnover rate vary with age. The aim of this study was to establish the laboratory reference range of serum bone-specific alkaline phosphatase (sBAP), serum type I collagen cross-linked C-terminal telopeptide (sCTx), and urine CTx (uCTx), based on values from 665 healthy Chinese women aged 20–80 years. We measured the levels of sBAP, sCTx, serum alkaline phosphatase (sALP), and uCTx and evaluated the age-related changes and their relationship with bone mineral density (BMD) in the anteroposterior (AP) lumbar spine, hip, and left forearm. We found significant correlations between biochemical markers and age, with coefficients of determination (R ²) of 0.358 for sBAP, 0.126 for sCTx, 0.125 for uCTx, and 0.336 for sALP. The net changes in different biochemical markers were inversely correlated with the rates of BMD loss in the AP lumbar spine. After correction for age, body weight, and height, the levels of the markers had significant negative correlations with the BMD of the AP lumbar spine, femoral neck, and ultradistal forearm. All four biochemical markers had the highest negative correlation with BMD of the AP lumbar spine (partial correlation coefficients of −0.366, −0.296, −0.290, and −0.258 for sBAP, sCTx, uCTx, and sALP, respectively). The mean and SD values of these markers in premenopausal and postmenopausal women with normal BMD values were used as the normal reference ranges. The reference ranges of sBAP, sCTx, and uCTx for pre- vs postmenopausal women were 17.3 ± 6.23 vs 18.9 ± 7.52 U/l, 3.18 ± 1.49 vs 3.23 ± 1.57 nmol/l, and 15.5 ± 11.4 vs 16.2 ± 12.4 nM bone collagen equivalents/mM urinary creatinine, respectively. Levels of the bone formation marker (sBAP) and bone resorption markers (sCTx, uCTx) increased rapidly in women with osteopenia or osteoporosis, indicating that they may be sensitive markers to determine the bone turnover rate in healthy Chinese women.