Decrease In NTx Research Articles

Denosumab is effective toward glucocorticoid-induced osteoporosis patients complicated with rheumatic diseases regardless of prior anti-osteoporotic drugs.

We examined the efficacy and safety of denosumab as treatment for glucocorticoid-induced osteoporosis (GIOP) patients complicated with rheumatic diseases, by measuring patients' lumber bone mineral density (BMD) and bone turnover markers. A total of 66 consecutive patients for whom denosumab was initiated between July 2013 and August 2016 were enrolled and evaluated for 12months. All of the patients were treated with glucocorticoids for underlying rheumatic diseases. The clinical assessment included measurements of the BMD of the lumbar spine (L2-L4) by a dual-energy X-ray absorptiometry technique and the bone turnover markers N-terminal telopeptide of type 1 collagen (NTX) in urine, serum intact procollagen type 1N-terminal propeptide (P1NP), and bone-specific alkaline phosphatase (BAP) at baseline, 6months and 12months after the start of denosumab treatment. Adverse events (AEs) until 12months were also analyzed. The mean percentage changes in BMD from baseline to 6 and 12months were significant (2.85% increase, p < 0.0001 and 4.40% increase, p < 0.0001, respectively) regardless of the prior anti-osteoporotic drugs treatment (16 no transition from anti-osteoporotic drugs, 27 transition from bisphosphonate, 23 transition from teriparatide). The decreases in NTX, P1NP and BAP at 6 and 12months were also significant. No serious AEs were noted. A multivariable logistic analysis showed that the prednisolone dose at baseline was associated with the clinical response to denosumab. In a real-world setting, denosumab was effective and safe for treating GIOP patients complicated with rheumatic diseases regardless of prior anti-osteoporotic drug treatment.

Preventive effect of zoledronic acid on aromatase inhibitor-associated bone loss for postmenopausal breast cancer patients receiving adjuvant letrozole

BackgroundThis study aims to compare the efficacy and safety between zoledronic acid combined with calcium and calcium alone to prevent aromatase inhibitor-associated bone loss for postmenopausal breast cancer patients receiving adjuvant letrozole.MethodsOne hundred twenty patients were randomly divided into two groups, A and B. Patients in group A (n=60) received modified radical mastectomy or breast-conserving surgery + four cycles of AC followed by T regimen (optional) + radiotherapy (optional) + letrozole 2.5 mg daily + calcium 500 mg twice daily + vitamin D 400 international units daily +4 mg of zoledronic acid every 6 months, while patients in group B (n=60) were not given zoledronic acid and the rest of the treatments of group B were the same as group A. All the patients were followed up for 1 year. The primary endpoint was the intrapatient percentage change in lumbar spine (LS) bone mineral density (BMD) from baseline to month 12. Secondary endpoints included the percentage change in total hip (TH) and femoral neck (FN) BMD, the incidence of osteoporosis, the incidence of a clinically meaningful 5% decline in BMD at 1 year, change of serum N-telopeptide of type 1 collagen (NTX) and bone-specific alkaline phosphatase (BSAP) concentrations.ResultsPatients in group A had a statistically significant higher average change and average percent change in LS, FN, and TH than group B. Group A had a statistically significant lower incidence of a clinically meaningful loss of bone density at the LS, FN, or TH than Group B. The incidence of osteoporosis in group A was significantly lower than group B. The decreases in NTX and BSAP concentrations from baseline to month 12 in patients of group A were significant; in contrast, patients in group B were found to have increases in NTX and BSAP concentrations from baseline. The most common adverse reactions in patients are flu-like symptoms (38%), bone pain (28%), and joint pain (20%).ConclusionAI-associated bone loss can be prevented by concurrent zoledronic acid for postmenopausal breast cancer patients.

Oxidative Stress and Raloxifene

Dear Editor, We read “Effects of raloxifene on bone metabolism in hemodialysis patients with type 2 diabetes” by Saito et al. (1) with a great interest. This paper shows that raloxifene works in diabetic or non-diabetic hemodialysis patients to reduce bone loss. This was shown by means of significant decrease in NTx and a significant increase in SOS measurements in both treatment groups compared to the un-treated control arms. We would like to draw attention to the possible anti-oxidant role of raloxifene regarding beneficial effects on the bone turnover markers as well as bone mass. The targeted population in this study consisted hemodialysis patients with type 2 diabetes who under a great oxidative stress related to both renal failure and diabetes (2, 3). We have previously demonstrated that women with post-menopausal osteoporosis had lower erythrocyte catalase (CAT) enzyme activity and higher erythrocyte malondialdehyde (MDA) levels (4). Interestingly, in another study we showed that raloxifene treatment for 3 months significantly enhanced CAT enzyme activity and reduced the MDA levels in women with PMO (5). Similar anti-oxidant effects of raloxifene were confirmed by others (6). Although neither discussed nor studied by means of enzymatic parameters, we would like to attract Authors’ attention to the potent anti-oxidant effect of raloxifene particularly in this special study population. Significant decrease in N-terminal cross-linking telopeptide of type I collagen (NTx) as well as oxidative stress parameters has been achieved with the use of potent anti-oxidants (lycopene) in patients with PMO (7). We think the results of this present study should also be admissible regarding the anti-oxidant effects of raloxifene particularly in hemodialysis patients with type 2 diabetes who are under great oxidative stress.

Effects of raloxifene on bone metabolism in hemodialysis patients with type 2 diabetes

BackgroundOsteoporosis and chronic kidney disease are common conditions in older adults, and often occur concurrently. Bone disease is caused by increased bone turnover accompanying secondary hyperparathyroidism, and by factors such as bone metabolic disorder accompanying kidney disease and postmenopausal or age-related osteoporosis, even in hemodialysis patients. Raloxifene is commonly used for the treatment of postmenopausal osteoporosis in the general population, and may be a treatment option for osteoporosis in hemodialysis patients. However, the effects of raloxifene in hemodialysis patients with type 2 diabetes have not been examined in detail.ObjectivesThis study was performed to investigate the effects of raloxifene on bone turnover markers and bone density in postmenopausal women with type 2 diabetes mellitus who were undergoing hemodialysis in Japan.Patients and MethodsThe subjects were 60 female patients on maintenance hemodialysis (non-diabetic, n=30; diabetic, n=30). Raloxifene hydrochloride (60 mg) was administered to 14 diabetic patients and 14 non-diabetic patients for one year, and these patients were compared with control groups (no raloxifene) of 16 diabetic patients and 16 non-diabetic patients. Serum levels of N-terminal cross-linking telopeptide of type I collagen (NTx), bone alkaline phosphatase, and intact parathyroid hormone (iPTH) were measured, and bone density was determined by quantitative heel ultrasound at the speed of sound (SOS) in the calcaneus during this period.ResultsThere were no significant differences in the levels of bone turnover markers except for iPTH after treatment of diabetic and non-diabetic patients with raloxifene for one year. SOS increased after treatment with raloxifene, but was significantly decreased in the control groups. Treatment with raloxifene resulted in a significant decrease in NTx and a significant increase in SOS in both diabetic and non-diabetic patients. There were no significant differences between the diabetic and non-diabetic patients who received raloxifene.ConclusionsTreatment with raloxifene can suppress reduction in bone density in postmenopausal women with type 2 diabetes who are undergoing hemodialysis.

Predictive implications of bone turnover markers after palliative treatment with 186Re-HEDP in hormone-refractory prostate cancer patients with painful osseous metastases

To prospectively evaluate the predictive value of various bone formation and resorption markers in patients with bone metastases from prostate cancer after palliative treatment with (186)Re-1,1-hydroxyethylidene diphosphonate ((186)Re-HEDP). Included in the study were 36 men with prostate cancer, suffering from painful osseous metastases and treated with (186)Re-HEDP. None had received any treatment that would have interfered with bone metabolism before (186)Re-HEDP treatment or throughout the follow-up period. For each patient, pretreatment and posttreatment serum levels of osteocalcin (OC), bone alkaline phosphatase (BALP), aminoterminal (PINP) and carboxyterminal (PICP) propeptides of type I collagen, amino-terminal (NTx) and carboxyterminal (CTx) telopeptides of type I collagen and their combinations were compared with the level and duration of pain response to radionuclide treatment. Pain response was correlated only with pretreatment NuTaux/PINP, PICP/PINP and NTx/CTx ratios and posttreatment decrease in baseline NTx and PICP values (p = 0.0025-0.035). According to multivariate and ROC analyses, the best marker-derived predictors of better and longer duration of response to (186)Re-HEDP treatment were a posttreatment decrease in NTx of > or = 20% (RR = 3.44, p = 0.0005) and a pretreatment NTx/PINP ratio of > or = 1.2 (RR = 3.04, p = 0.036) NTx, a potent collagenous marker of bone resorption, along with the novel NTx/PINP ratio provide useful cut-off values for identifying a group of patients suffering from painful osseous metastases from hormone-refractory prostatic carcinoma who do not respond to palliative treatment with (186)Re-HEDP. This information could help avoid an inefficient and expensive radionuclide treatment. Also, in the cohort of patients who will eventually undergo such treatment, the medium-term posttreatment changes in NTx offer valuable predictive information regarding long-term palliative response.

The Effects of Creatine and Protein Supplementation on Bone Catabolism in Older Men

Recent evidence suggests that creatine supplementation may have beneficial effects on bone. PURPOSE: To determine the effect of low-dose creatine combined with protein supplementation during resistance training on a marker of bone catabolism (N-telopeptide cross-links of type I collagen) in healthy older men. METHODS: Men (65.4±4.7y) were randomized (double blind) to receive either 0.1 g/ kg body mass/d creatine (n=13), 0.1 g/kg body mass/d creatine and 0.3 g/kg body mass/d protein (n=7), or protein only (n=11) for 10 weeks. Subjects ingested their supplements 3 days per week, with half of the supplement ingested before, and half ingested after performing a bout of whole-body resistance training. Twentyfour hour urine samples were collected before and after the 10 weeks of training and supplementation and analyzed by ELISA for N-telopeptide cross links of type I collagen (NTx). RESULTS: There were no signficant group x time interactions for absolute changes (changes from pre to post were: Creatine group 59±25 to 45±25; Creatine + Protein group 56±26 to 35±24; Protein group 51±27 to 47±23 nM BCE/ mM creatinine). When the groups receiving creatine were combined, they had a greater relative decrease in NTx compared to the protein group (−24±20% vs. +13±82%; p=0.05). CONCLUSIONS: Creatine supplementation during a resistance training program is beneficial for reducing bone catabolism in older men. Supported by Experimental and Applied Sciences (EAS)

Treatment of anorexia nervosa is associated with increases in bone mineral density, and recovery is a biphasic process involving both nutrition and return of menses

Background: Recovery from osteoporosis in anorexia nervosa (AN) is uncertain.Objective: The purpose of this study was to understand the changes in bone mineral density (BMD) in women with AN and the mechanisms of recovery from osteopenia.Design: We studied BMD and markers of bone formation and resorption, osteocalcin and N-telopeptide (NTX), in patients with AN (n = 28) who were following a behavioral weight-gain protocol.Results: Anorexic patients experienced significant percentage increases in BMD (4.38 ± 7.48% for spine; 3.77 ± 8.8% for hip; P< 0.05 for both) from admission until recovery of 90% ideal body weight, achieved over 2.2 mo. NTX concentrations were higher in patients with AN at admission than in healthy control subjects (n =11; 69.0 ± 31.09 and 48.3 ± 14.38 nmol/mmol creatinine, respectively; P< 0.05) and in reference control subjects (n = 30; 69.0 ± 31.09 and 37.0±6.00 nmol/mmol creatinine, respectively; P< 0.001). In weight-recovered subjects with AN, osteocalcin increased (from 8.0 ± 3.05 to 11.2 ± 6.54 ng/mL; P< 0.05), whereas NTX remained elevated (from 69.0 ± 31.09 to 66.7 ± 45.5 nmol/mmol creatinine; NS). A decrease in NTX (from 70.7 ± 40.84 to 45.9 ± 22.72 nmol/mmol creatinine; NS) occurred only in the subgroup of subjects who regained menses with weight recovery.Conclusions: Nutritional rehabilitation induces a powerful anabolic effect on bone. However, a fall of NTX and a shift from the dominant resorptive state, which we postulate involves full recovery, may involve a hormonal mechanism and require a return of menses. Nutritional rehabilitation appears to be critical to bone recovery and may explain the ineffectiveness of estrogen treatment alone on BMD in the cachectic state.

Effect of zoledronic acid on markers of bone turnover and mineral density in osteoporotic patients with beta-thalassaemia

Osteoporosis has emerged as an important cause of morbidity in patients with thalassemia major. Studies regarding the efficacy of bisphosphonates in thalassemia-induced osteoporosis have yielded conflicting results. We performed this prospective study to evaluate the efficacy of zoledronic acid in osteoporotic patients with thalassemia major. Patients, 29, were given 1 mg zoledronic acid intravenously every 3 months for a total of four doses. Twenty age- and sex-matched healthy blood donors served as controls. Before each infusion and 3 months after the last infusion, we determined serum levels of osteoprotegerin (OPG), N-terminal cross-linking telopeptide of type I collagen (NTX), osteocalcin (OC) and insulin-like growth factor 1 (IGF-1). Bone mineral density (BMD) of the lumbar spine was measured at baseline and after the treatment's completion. At baseline, OPG did not differ significantly between patients and controls (p=0.2), NTX were higher in patients although not significantly (p=0.139), whereas, OC levels were significantly higher and IGF-1 levels significantly lower in patients than in controls (p<0.001 and p<0.006, respectively). Zoledronic acid administration resulted in a significant decrease in NTX, OC and IGF-1 (p<0.05, p<0.001 and p<0.05, respectively) and in a significant increase in OPG and BMD (p<0.05 for both comparisons). The change in NTX, osteocalcin and IGF-1 became significant as early as 3 months after the first administration of zoledronic acid, while the change in OPG reached significance only after three infusions. Our study supports the effectiveness of bisphosphonates in the treatment of thalassemia-induced osteoporosis.

Reversal of adverse effects of neoadjuvant chemotherapy on bone turnover in pre- and post-menopausal women with zoledronic acid

556 Background: Ovarian failure secondary to adjuvant chemotherapy is known to have an adverse effect on bone mineral density and to increase bone turnover markers. The effects of chemotherapy with growth factor support in the absence of hormonal changes have not been described. The impact of zoledronic acid on these changes was also explored. Methods: We evaluated bone turnover markers in 82 women undergoing neoadjuvant chemotherapy for localized stage II/III breast cancer at initial diagnosis prior to treatment and after 4 cycles of epirubicin (75mg/m2)-docetaxel (75mg/m2) with pegylated G-CSF support with or without zoledronic acid. 47% of patients were post-menopausal and all groups were balanced for other variables. Women were randomized to receive zoledronic acid 4 mg IV every 3 weeks concurrently with chemotherapy (n=41) versus no bisphosphonate treatment (n=41). Bone turnover markers included: urinary N-telopeptide (NTx), serum bone specific alkaline phosphatase (BAP)and osteocalcin (OSTEO). Results: Women, regardless of menopausal status, who received no bisphosphonate had statistically significant increases in NTx, from baseline after 3 months of neoadjuvant chemotherapy using multivariable mixed repeated measures (p=0.0213). Women who received zoledronic acid concurrently with neoadjuvant chemotherapy had statistically significant decreases in NTx (p&lt;0.0001), BAP (p&lt;0.0001) and OSTEO (p=0.0295) from baseline. This is the first demonstration that anthracycline-taxane chemotherapy with growth factor support increased bone turnover markers in both post-menopausal and pre-menopausal women independent of hormone therapy, radiation therapy and surgery. Conclusions: Neoadjuvant chemotherapy with anthracycline- taxane and growth factor support increased bone resorption markers in both post-menopausal and pre-menopausal women. Zoledronic acid given concurrently with each cycle of chemotherapy reversed this increase in bone turnover markers. No significant financial relationships to disclose.

Impact of lowering dialysate calcium concentration on serum bone turnover markers in hemodialysis patients

Loss of renal function perturbs bone metabolism because kidney is a vital organ maintaining homeostasis of calcium and phosphate. In hemodialysis patients, bone diseases are serious complications resulting in fractures and extraosseous calcification. The latest clinical practice guidelines by the National Kidney Foundation (New York, US) recommend a dialysate calcium concentration (D-Ca) of 2.5 mEq/L rather than 3.0 mEq/L to avoid excess calcium load and to prevent subsequent vascular calcification. However, there is no perfect agreement yet about which concentration should be chosen because lowering D-Ca might enhance uncoupled bone resorption. Here, we studied effects of lowering D-Ca from 3.0 to 2.5 mEq/L on bone metabolism in 67 patients. Doses of vitamin D and phosphate binders were kept constant for a 2-month period beginning 1 month before the change in D-Ca, and were adjusted thereafter. In group A [intact parathyroid hormone (iPTH) < 100 pg/ml before the study], serum cross-linked N-terminal telopeptide of type I collagen (NTx) increased immediately after lowering D-Ca and then remained stable. Intact osteocalcin (iOC) increased later along with iPTH, suggesting the improvement of adynamic bone disease which shows a marked decrease in bone turnover without osteoid accumulation. Vitamin D was not dosed up in this group. In group B (100 ≤ iPTH < 300), serum NTx increased transiently, which is followed by an increase of iOC but not by a change of iPTH. In group C (300 ≤ iPTH), lowering D-Ca allowed us to increase the dose of vitamin D without hypercalcemia, leading to a significant decrease in NTx and iPTH. Overall, serum phosphate increased from 5.4 ± 1.6 to 6.1 ± 1.6 mg/dL ( P < 0.0001) and serum NTx increased by 1.5-fold ( P < 0.0001) 1 month after lowering D-Ca. Over a 3-month period after that, serum phosphate and serum NTx decreased to their basal levels. These indicate that bone resorption predominated over formation for only a short period. In conclusion, a D-Ca of 2.5 mEq/L with adjustment of vitamin D ameliorates metabolic abnormalities of bone which develop under 3.0 mEq/L.

The effect of Risedronate sodium hydrate (benet®) in patients with or without asthma, employing different doses of steroid

RATIONALE: Although majority of patients are now well controlled wiith inhaled corticosteroids, some asthmatics still require oral stroids either on daily or as needed basis.Evaluation of the effect of Risedronate sodium hydrate on osteoporosis was carried out in asthma and non-asthma patients requiring steroid therapy in one form or another METHODS: Patients whose biochemical bone resorption marker, serum cross-linked collagen N-peptides(serum NTx)was below 14nM BCE/L and/or the bone mineral density(BMD) below 80% young adult mean(YAM) employing digital image processing(DIP)were asked to join a follow up study to take Risedronate sodium hydrate for 8 to 48 weeks. Sixty patients finished the study,13 males and 47 females. Four dropped out,2 due to aggravation of original disease and 2 due to side effects. Twenty two had asthma, all on some form of steroids,while 38 was non-asthmatics, 28 without and 10 with steroids.The patients were grouped into those using oral steroids on daily basis(A),oral steroids only as needed(B),only on inhaled corticosteroid(C),and those without steroid(D) RESULTS: NTx level showed no correlations to any of the factors except age showing favorable response in younger age group upon taking Risedronate. However,when analyzed within female participants,it was found that those on oral steroid (group A+B)responded significantly better to Risedronate sodium hydrate than those on inhaled corticosteroids or those without any steroids(group C+D).(p value:0.029).None of the factors were found to correlate with the bone mineral density assessed by DIP CONCLUSIONS: Significant decrease in NTx after oral Risedronate in females requiring oral steroids suggest its advantage in severe female asthmatics on current oral corticosteorids.

A Toxicity Profile of Osteoprotegerin in the Cynomolgus Monkey

Osteoprotegerin (OPG) is a novel secreted glycoprotein of the tumor necrosis factor (TNF) receptor superfamily that acts as an antiresorptive agent inhibiting osteoclast maturation. OPG acts by competitively inhibiting the association of the OPG ligand with the RANK receptor on osteoclasts and osteoclast precursors. This inhibition of osteoclasts can lead to excess accumulation of newly synthesized bone and cartilage in vivo. The purpose of this study was to investigate the potential toxicity of a human recombinant form of OPG in the young cynomolgus monkey. OPG was administered by intravenous (IV) or subcutaneous (SC) injection three times per week for either 4 or 13 weeks. There were no deaths during the study, no clinical signs related to treatment, no effect on body weight, appetence, or ophthalmology. No toxicologically relevant changes in routine laboratory investigations, organ weights, or gross or histopathological findings were observed. Serum ionized calcium and phosphorus were decreased at all dose levels. Evaluations were performed to monitor biochemical markers of bone resorption (N-telopeptide [NTx], deoxypyridinoline [DPD]), bone formation (skeletal alkaline phosphatase [s ALP], osteocalcin [OC]), parathyroid hormone [PTH], and bone density of the proximal tibia and distal radius in vivo. Dose-related decreases in NTx and/or DPD were observed at each dose level, with up to a 90% decrease in NTx noted for animals treated IV or SC at 15 mg/kg. Similar decreases were observed for s ALP and OC. PTH was increased for animals treated at 5 and 15 mg/kg (IV or SC). Trabecular bone density was increased for the majority of males and females treated IV or SC at 15 mg/kg and males treated IV at 5 mg/kg. Microscopic examination of the sternebrae revealed corresponding increases in bone. Decreases in markers of bone turnover, and corresponding increases in bone density, were consistent with the pharmacological action of OPG as an osteoclast inhibitor. The no-observable-adverse-effect level (NOAEL) of OPG was 15 mg/kg.

A toxicity profile of osteoprotegerin in the cynomolgus monkey.

Osteoprotegerin (OPG) is a novel secreted glycoprotein of the tumor necrosis factor (TNF) receptor superfamily that acts as an antiresorptive agent inhibiting osteoclast maturation. OPG acts by competitively inhibiting the association of the OPG ligand with the RANK receptor on osteoclasts and osteoclast precursors. This inhibition of osteoclasts can lead to excess accumulation of newly synthesized bone and cartilage in vivo. The purpose of this study was to investigate the potential toxicity of a human recombinant form of OPG in the young cynomolgus monkey. OPG was administered by intravenous (i.v.) or subcutaneous (s.c.) injection three times per week for either 4 or 13 weeks. There were no deaths during the study, no clinical signs related to treatment, no effect on body weight, appetence, or ophthalmology. No toxicologically relevant changes in routine laboratory investigations, organ weights, or gross or histopathological findings were observed. Serum ionized calcium and phosphorus were decreased at all dose levels. Evaluations were performed to monitor biochemical markers of bone resorption (N-telopeptide [NTx], deoxypyridinoline [DPD]), bone formation (skeletal alkaline phosphatase [sALP], osteocalcin [OC]), parathyroid hormone [PTH], and bone density of the proximal tibia and distal radius in vivo. Dose-related decreases in NTx and/or DPD were observed at each dose level, with up to a 90% decrease in NTx noted for animals treated i.v. or s.c. at 15 mg/kg. Similar decreases were observed for sALP and OC. PTH was increased for animals treated at 5 and 15 mg/kg (i.v. or s.c.). Trabecular bone density was increased for the majority of males and females treated i.v. or s.c. at 15 mg/kg and males treated i.v. at 5 mg/kg. Microscopic examination of the sternebrae revealed corresponding increases in bone. Decreases in markers of bone turnover, and corresponding increases in bone density, were consistent with the pharmacological action of OPG as an osteoclast inhibitor. The no-observable-adverse-effect level (NOAEL) of OPG was 15 mg/kg.

Clinical usefulness of biochemical resorption markers in osteoporosis.

We have evaluated three commercial assays for collagen cross-links, two urine assays and a recently developed serum assay, as markers of bone turnover in 30 postmenopausal women with osteoporosis during their first year of treatment with the anti-resorptive drug alendronate. Before treatment, urine free deoxypyridinoline crosslinks (Dpd), urine N-telopeptide crosslinks (NTx) and serum C-telopeptide (CTx) values were within postmenopausal reference ranges. After 3 months' treatment the decrease in NTx and CTx was greater than that of Dpd (-50%, P < 0.0001 and -48%, P < 0.0001, compared with -11%, NS), as it was after 6 months (-51%, P < 0.0001, and -57%, P < 0.0001, compared with -19%, P < 0.01). The decrease in resorption markers after 6 months was significant in 23% (Dpd), 66% (NTx) and 66% (CTx) of individuals. Neither baseline resorption marker values nor the per cent change after 6 months' therapy correlated with bone mineral density change (BMD) at either lumbar spine or femoral neck after one year's therapy, except baseline Dpd and lumbar spine BMD (P < 0.01). We conclude that NTx and serum CTx were more sensitive markers of bone turnover suppression by alendronate, but only baseline Dpd was useful in the prediction of individual bone density response after one year.

Hormone Replacement Therapy in Postmenopausal Women: Urinary N-Telopeptide of Type I Collagen Monitors Therapeutic Effect and Predicts Response of Bone Mineral Density

PURPOSE: To assess the ability of the urinary N-telopeptide of type I collagen (NTx) to monitor and predict therapeutic effects of hormone replacement therapy (HRT) in postmenopausal women.PATIENTS AND METHODS: To assess the relationship between baseline or change in NTx (predictive variable), and change in lumbar and hip bone mineral density (BMD; outcome variable), we conducted a 2-year randomized controlled study at academic university and private practice medical centers in 236 healthy women 1 to 3 years postmenopausal; 227 women completed the study. Women received estrogen plus progesterone plus calcium (treated group) or calcium alone (control group).RESULTS: In the treated group NTx significantly (P <0.0001) decreased, and spine and hip BMD significantly (P <0.00001 and P <0.005, respectively) increased; in the control group NTx did not change but BMD decreased significantly (P <0.01). Subjects in the highest quartiles for baseline NTx (67 to 188 units) or decreasing NTx (−66% to −87%) through 6 months demonstrated the greatest gain in BMD in response to HRT (P <0.05 and P <0.005). For every increase of 30 units in baseline NTx, the odds of gain in BMD in response to HRT increased by a factor of 5.0 (95% confidence interval [CI] 1.9 to 13.3); for every 30% decrease in NTx through 6 months, the odds of gaining BMD in response to HRT increased by a factor of 2.6 (95% CI 1.6 to 4.4). In the control group an increase of 30 units in mean NTx across the study indicated a higher odds of losing BMD by a factor of 3.2 (95% CI 1.6 to 6.5). A high baseline NTx (>67 units) indicated a 17.3 times higher risk of BMD loss if not treated with HRT.CONCLUSION: These data support the clinical utility of NTx to monitor the antiresorptive effect of HRT in recently postmenopausal women, and to predict changes in BMD in response to HRT.