Changes In Bone Turnover Markers Research Articles

Four-year Results of a Phase 2 Study of the Cathepsin K Inhibitor Odanacatib in Postmenopausal Women with Low Bone Mineral Density: Effects on Bone Mineral Density and Bone Turnover Markers

Monthly oral ibandronate is indicated for the prevention and treatment of osteoporosis in postmenopausal women. The STudy Researching Osteoporosis iN Guys (STRONG) investigated the efficacy and safety of 150-mg monthly oral ibandronate in men with primary, idiopathic, or hypogonadism-related low bone density.STRONG was a 1-year, placebo-controlled, randomized (2 ibandronate: 1 placebo), double-blind study that enrolled ambulatory men aged ≥ 30 years with baseline femoral neck (FN) bone mineral density (BMD) T-scores ≤ − 2.0 and lumbar spine (LS) BMD T-scores ≤ − 1.0 or LS BMD T-scores ≤ − 2.0, FN BMD T-scores ≤ − 1.0, and BMD T-scores ≥ − 4.0 at any site assessed by dual-energy X-ray absorptiometry. The primary endpoint was mean percent change from baseline in LS BMD at 1 year (intent-to-treat [ITT] population). Secondary endpoints included mean BMD changes from baseline at the FN, total hip (TH), and trochanter (TR) and changes in bone turnover markers (BTMs), as measured by the bone resorption marker serum C-terminal telopeptide of type 1 collagen (sCTX) and the bone formation marker bone-specific alkaline phosphatase (BSAP). All men received twice daily calcium carbonate (1000 mg/day) and vitamin D (400 IU/day). Changes in BMD for treatment groups were compared using analysis of covariance with treatment, investigative site, and baseline testosterone as factors and baseline BMD as a covariate.The ITT population consisted of 132 men; 47 received placebo and 85 received monthly ibandronate. Men who received ibandronate achieved greater increases in LS BMD at 12 months than those who received placebo (3.5% vs. 0.9%, respectively; difference, 2.6; p < 0.001). The ibandronate group also achieved greater 12-month BMD increases than the placebo group, respectively, at the TH (1.8% vs. − 0.3%; difference, 2.1; p < 0.001), FN (1.2% vs. − 0.2%; difference, 1.4; p = 0.012), and TR (2.2% vs. 0.4%; difference, 1.7; p < 0.005). In men who completed the study and adhered to the protocol (per-protocol (PP) population), percent decreases in median sCTX and BSAP levels from baseline were also greater with ibandronate versus placebo (p ≤ 0.001 for both comparisons). Overall, monthly ibandronate was well tolerated.In men with low BMD, 1 year of treatment with oral once-monthly 150-mg ibandronate significantly increased BMD at the LS and hip (TH, TR, and FN), significantly reduced BTM levels in the PP population, and was generally well tolerated.

Early Changes in Bone Specific Turnover Markers During the Healing Process After Vertebral Fracture

Background:The present study measured longitudinal changes in bone turnover markers in elderly patients with vertebral fracture and investigated the relationship among bone turnover markers, duration of bed rest and bone mineral density (BMD).Methods:Criteria for patient selection were 50 years in age and older, and presence of VF. Serum bone-specific alkaline phosphatase (BAP) was measured as a marker of bone formation. Urinary crosslinked N-terminal telopeptides of type I collagen (NTX) was measured as a marker of bone resorption. In principle, samples were collected just after injury, within 24 h, and 1, 2, 3, 5 and 8 weeks after. We also measured duration of bed rest and BMD.Results:The study population consisted of 42 cases. The average BMD of the lumbar vertebrae was 0.670 ± 0.174 g/cm2. Bed rest period was 17.9 ± 8.8 days. BAP showed significantly higher values at 2 and 3 weeks compared with the baseline value. Thereafter, BAP progressively decreased until 8 weeks. Urinary NTX was increased soon after the onset of pain with the same patterns in BAP. Urinary NTX values reached a peak at 3 weeks, and then they kept significantly higher values until 8 weeks. The peak value of serum BAP was affected by the duration of bed rest, although that of the urinary NTX was not. The peak values of serum BAP and urinary NTX showed negative correlations with the initial BMD values.Conclusions:Bone turnover markers remained higher at 8 weeks, even patients symptom was healed after VF. Bone turnover markers were affected on physical activity and BMD.

Effects of calcium-fortified ice cream on markers of bone health

Premenopausal women with low calcium intakes consumed calcium-fortified ice cream daily for 28days. Bone markers, NTX, CTX and PTH decreased significantly by 7days, with some evidence of a calcium dose-dependent effect. Bone marker responses were observed within 1h of consuming ice cream. Body weight remained constant over 28days. Dietary calcium is important for lifelong bone health. Milk is a good source of bioavailable calcium, but consumption has declined among young adults. The aims were to determine whether calcium-fortified ice cream, a palatable source of calcium, produces significant, sustainable changes in bone turnover markers and parathyroid hormone (PTH) in premenopausal women with calcium intake below recommended UK levels. Eighty women, ages 20-39years (calcium intake <750mg/day) were randomised to consume lower saturated fat/sugar ice cream containing 96, 244, 459 or 676mg calcium daily for 28days. Urinary NTX/Cr, serum CTX, PINP, 1,25D and PTH were measured (baseline, days1, 7 and 28). Acute changes in CTX and PTH were measured over 5h (n = 29 women). There were significant mean decreases by 7days in NTX/Cr, CTX, PTH and 1,25D and increases in PINP (one sample t tests), with a significant dose-dependent effect on CTX analysis of covariance. Only CTX remained suppressed at 28days. Serum CTX and PTH decreased within 1h. Body weight did not change significantly between baseline and 28days. Daily consumption of calcium-fortified ice cream by premenopausal women may significantly reduce levels of the bone resorption marker serum CTX, without stimulating weight gain. The ice cream could be incorporated into the diet to replace low-calcium snacks and thus help individuals with habitually low calcium intakes to meet recommended intakes. The 244mg calcium preparation would provide more than a quarter of the UK daily recommended nutrient intake for premenopausal women.

Differential effects of teriparatide on regional bone formation using 18F-fluoride positron emission tomography

Teriparatide increases skeletal mass, bone turnover markers, and bone strength, but local effects on bone tissue may vary between skeletal sites. We used positron emission tomography (PET) to study (18)F-fluoride plasma clearance (K(i)) at the spine and standardized uptake values (SUVs) at the spine, pelvis, total hip, and femoral shaft in 18 postmenopausal women with osteoporosis. Subjects underwent a 1-hour dynamic scan of the lumbar spine and a 10-minute static scan of the pelvis and femurs at baseline and after 6 months of treatment with 20 µg/day teriparatide. Blood samples were taken to derive the arterial input function and lumbar spine K(i) values evaluated using a three-compartment model. SUVs were calculated for the spine, pelvis, total hip, and femoral shaft. After 6 months treatment with teriparatide, spine K(i) values increased by 24% (p = .0003), while other model parameters were unchanged except for the fraction of tracer going to bone mineral (k(3)/[k(2) + k(3)]), which increased by 23% (p = .0006). In contrast to K(i) , spine SUVs increased by only 3% (p = .84). The discrepancy between changes in K(i) and SUVs was explained by a 20% decrease in (18)F(-) plasma concentration. SUVs increased by 37% at the femoral shaft (p = .0019), 20% at the total hip (p = .032), and 11% at the pelvis (p = .070). Changes in bone turnover markers and BMD were consistent with previous trials. We conclude that the changes in bone formation rate during teriparatide treatment as measured by (18)F(-) PET differ at different skeletal sites, with larger increases in cortical bone than at trabecular sites.

Serum Levels of Bone Turnover Markers following Total Joint Arthroplasty

To evaluate changes in serum levels of bone turnover markers during the first year following a total hip or knee arthroplasty (THA or TKA, respectively). 34 women and 13 men (mean age, 68 years) with idiopathic hip or knee osteoarthritis underwent elective THA or TKA. The serum levels of (1) osteoprotegerin, (2) nuclear factor-kappa B ligand (RANKL), (3) osteocalcin, and (4) bone-specific alkaline phosphatase (b-ALP) were determined in each patient on preoperative day 1 and postoperative day 3 and 7, and month 2, 4, 6, 8, 10, and 12. All 4 markers changed significantly over the 12-month period. At month 12, values of all markers did not return to their preoperative levels uniformly. At month 8, the serum levels of osteoprotegerin, osteocalcin, and b-ALP remained higher than their respective preoperative values. The serum levels of RANKL gradually decreased after month 2, rendering this marker a potential index for fixation. Bone turnover markers change following arthroplasties. Postoperative month 8 seems to be a milestone in the normal course of these markers.

Seasonal variation of bone turnover markers in top-level female skiers

Different levels of weight-bearing activities imply different levels of anabolic effects on skeletal tissue and this can be assessed by measuring biochemical markers reflecting bone metabolism. With this study we wanted to determine how the serum levels of bone turnover markers change during different phases of annual training in elite female skiers. Fourteen top-level Caucasian athletes, from the Italian Women's Alpine Ski Team (slalom and giant slalom), were tested at the end of the relative rest period (T1), the pre-competitive season (T2) and the competitive season (T3). Serum levels of bone-specific alkaline phosphatase (BAP) and tartrate-resistant acid phosphatase (TRAP5b) activities and of osteocalcin (OC), and crosslaps (the carboxyterminal crosslinked telopeptide of type I collagen--β-CTx), were assayed together with the determination of 25(OH)D levels. The formation markers, BAP and OC and the resorption marker TRAP5b significantly increased from T2 to T3, while crosslaps showed no significant changes. The peculiar trends of bone formation markers correlated one to each other at T2 versus T3, and this was probably linked to the highly demanding period of competitions when, in athletes performing weight-bearing exercise, bone is more stimulated by mechanical forces. 25(OH)D levels, instead, changed from T1 to T2 and from T1 to T3 and its trend do not show any correlation with that of bone markers. In conclusion, we found that both the bone formation markers and TRAP5b, marker of resorption, are significantly increased from the pre-competitive season to the competitive season.

Reversal of skeletal effects of endocrine treatments in the Intergroup Exemestane Study

The adjuvant use of aromatase inhibitors in breast cancer is associated with adverse effects on bone health. We previously reported a decline in bone mineral density (BMD) following the switch from tamoxifen to exemestane in the Intergroup Exemestane Study (IES). Here we report effects of endocrine treatment withdrawal on BMD, bone turnover markers (BTM) and fracture rates. 4,724 patients took part in IES, and 206 patients were included in a bone sub-study. BMD and BTM were assessed pre-randomization, during and after the end of treatment (EOT). To evaluate treatment withdrawal effects, 12- and 24-month post EOT BMD results are available for 122 and 126 patients, respectively. Similar patient numbers had BTM measured post EOT. Following treatment withdrawal, the differences in BMD observed between the two endocrine strategies were partially reversed. At 24 months from EOT, spine BMD increased by 1.53% (95%CI 0.63-2.43; p = 0.001) after stopping exemestane and fell by 1.93% (95%CI -2.91 to 0.95; p = 0.0002) following tamoxifen withdrawal. A similar pattern of changes was observed at the hip. At 2 years post EOT, BMD changes from baseline were similar with both treatment strategies. Corresponding inverse changes in BTM were seen, with an increase following tamoxifen withdrawal and a reduction after exemestane. A higher number of fractures occurred during exemestane treatment, but fracture rates were similar after treatment withdrawal. With the switch strategy used in IES, the on treatment adverse bone effects of exemestane are reversed. Ongoing monitoring of BMD is therefore not routinely required.

Influence of Long-Term Thromboprophylaxis With Low-Molecular-Weight Heparin (Enoxaparin) on Changes of Bone Metabolism Markers in Pregnant Women

This is a first descriptive, retrospective, observational study aiming to evaluate the changes in bone turnover markers in pregnant women and to assess the effect of a long-term treatment with low-molecular-weight heparin (LMWH), specifically, enoxaparin. Study involved 50 pregnant Caucasian women with thrombophilia. The patients either received prophylactic enoxaparin once daily subcutaneously (N = 35) or were observed without treatment (N = 15). Concentrations of total serum alkaline phosphatase (total AP), bone alkaline phosphatase (bone AP), osteoprotegerin (OPG), and the receptor activator of nuclear factor κB ligand (RANKL) were measured at 15, 25, and 35 weeks of gestation. Total serum AP increased with gestational age. In the group treated with enoxaparin, the percentage of bone AP concentration was lower (P < .05) than in the control group. Serum OPG also increased with gestational age, but no significant difference was found between the groups with- and without treatment. Despite the OPG increased, RANKL did not change.

P.1.c.040 Impulsive aggression in a patient treated with levetiracetam

To investigate the effects of prior treatment and determine the predictors of a 12-month treatment response of romosozumab (ROMO) in 148 patients with postmenopausal osteoporosis.In this prospective, observational, and multicenter study, treatment naïve patients (Naïve; n = 50) or patients previously treated with bisphosphonates (BP; n = 37) or denosumab (DMAb; n = 45) or teriparatide (TPTD; n = 16) (mean age, 75.0 years; T-scores of the lumbar spine [LS] −3.2 and total hip [TH] −2.6) were switched to ROMO due to insufficient effects of prior treatment. Bone mineral density (BMD) and serum bone turnover markers were evaluated for 12 months.At 12 months, changes in LS BMD were Naïve (18.2%), BP (10.2%), DMAb (6.4%), and TPTD (11.2%) (P < 0.001 between groups) and changes in TH BMD were Naïve (5.6%), BP (3.3%), DMAb (0.6%), and TPTD (4.4%) (P < 0.01 between groups), respectively. In all groups, the LS BMD significantly increased from baseline at 6 and 12 months, although only the DMAb group failed to obtain a significant increase in TH BMD during 12-month treatment. Mean values of N-terminal type I procollagen propeptide (PINP; μg/L) from baseline → 1 month → 12 months were Naïve (67.9 → 134.1 → 51.0), BP (32. 2 → 81.7 → 40.9), DMAb (30.4 → 56.2 → 75.3), and TPTD (97.4 → 105.1 → 37.1), and those of isoform 5b of tartrate-resistant acid phosphatase (TRACP-5b; mU/dL) were Naïve (500.4 → 283.8 → 267.1), BP (273.4 → 203.1 → 242.0), DMAb (220.3 → 246.1 → 304.8), and TPTD (446.6 → 305.1 → 235.7), respectively. Multiple regression analysis revealed that the significant predictors of BMD change at 12 months were difference of prior treatment (r = −2.8, P < 0.001) and value of PINP at 1 month (r = 0.04, P < 0.01) for LS, and difference of prior treatment (r = −1.3, P < 0.05) and percentage change of TRACP-5b at 1 month (r = −0.06, P < 0.05) for TH.The early effects of ROMO on LS and TH BMD increase at 12 months were significantly affected by the difference of prior treatment and are predicted by the early change in bone turnover markers.

Low bone density and bone metabolism alterations in Duchenne muscular dystrophy: response to calcium and vitamin D treatment

Boys with Duchenne muscular dystrophy often have reduced bone mass and increased fracture risk. In this prospective study on 33 patients, calcifediol (25-OH vitamin D(3)) plus adjustment of dietary calcium to the recommended dose reduced bone resorption, corrected vitamin D deficiency, and increased bone mass in about two-thirds of cases. Low BMC and BMD and bone metabolism alterations are frequent in boys with Duchenne muscular dystrophy (DMD), especially now that long-term glucocorticosteroid (GC) treatment is the standard of care. This prospective study was designed to evaluate the effects of a first-line treatment (25-OH vitamin D(3) [calcifediol] plus adjustment of dietary calcium to the recommended daily dose) on bone. Thirty-three children with DMD on GC treatment were followed for 3 years: one of observation and two of treatment. spine and total body BMC and BMD increase; secondary outcome: changes in bone turnover markers (C-terminal [CTx] and N-terminal [NTx] telopeptides of procollagen type I; osteocalcin [OC]). During the observation year, BMC and BMD decreased in all patients. At baseline and after 12 months, serum CTx and urinary NTx were higher than normal; OC and parathyroid hormone at the upper limit of normal; 25-OH vitamin D(3) significantly lower than normal. After 2 years of calcifediol and calcium-rich diet, BMC and BMD significantly increased in over 65% of patients, and bone metabolism parameters and turnover markers normalized in most patients (78.8%). During the observation year, there were four fractures in four patients, while during the 2 years of treatment there were two fractures in two patients. Calcifediol plus adequate dietary calcium intake seems to be an effective first-line approach that controls bone turnover, corrects vitamin D deficiency, and increases BMC and BMD in most patients with DMD. Lack of response seems related to persistently high bone turnover.

Assessment of regional changes in skeletal metabolism following 3 and 18 months of teriparatide treatment

Teriparatide (TPTD) increases skeletal mass, bone turnover markers, and bone strength, but in vivo effects at individual skeletal sites have not been characterized. Quantitative radionuclide imaging studies reflect bone blood flow and osteoblast activity to assess regional changes in bone metabolism. Changes in bone plasma clearance using technetium-99m methylene diphosphonate ((99m)Tc-MDP) were quantified and correlated with changes in bone turnover markers in 10 postmenopausal women with osteoporosis. Subjects underwent bone scintigraphy at baseline and 3 and 18 months after initiating TPTD 20 microg/day subcutaneously. Subjects were injected with 600 MBq (99m)Tc-MDP, and whole-body bone scan images were acquired at 10 minutes and 1, 2, 3, and 4 hours. Multiple blood samples were taken between 5 minutes and 4 hours after treatment, and free (99m)Tc-MDP was measured using ultrafiltration. The Patlak plot method was used to evaluate whole-skeleton (99m)Tc-MDP plasma clearance (K(bone)) and derive regional bone clearance for the calvarium, mandible, spine, pelvis, and upper and lower extremities using gamma camera counts. Bone turnover markers were measured at baseline and 3, 12, and 18 months. Median increases from baseline in whole-skeleton K(bone) were 22.3% (p = .004) and 33.7% (p = .002) at 3 and 18 months, respectively. Regional K(bone) values were increased significantly in all six subregions at 3 months and in all subregions except the pelvis at 18 months. Bone markers were increased significantly from baseline at 3 and 18 months and correlated significantly with whole-skeleton K(bone). This is the first study showing a direct metabolic effect of TPTD at different skeletal sites in vivo, as measured by tracer kinetics.

Administration of growth hormone in selectively protein-deprived rats decreases BMD and bone strength

Introduction Isocaloric protein undernutrition is associated with decreased bone mass and decreased bone strength, together with lower IGF-I levels. It remains unclear whether administration of growth hormone (GH) corrects these alterations in bone metabolism. Materials and methods Six-month-old female rats were fed isocaloric diets containing either 2.5% or 15% casein for 2 weeks. Bovine growth hormone (bGH, 0.5 or 2.5 mg/kg of body weight) or vehicle was then administered as subcutaneous injections, twice daily, to rats on either diet for 4 weeks. At the proximal tibia, analysis of bone mineral density (BMD), maximal load and histomorphometry were performed. In addition, urinary deoxypyridinoline, plasma osteocalcin and IGF-I concentrations were measured. Weight was monitored weekly. Results bGH caused a dose-dependent increase in plasma IGF-I regardless of the dietary protein content. However, bGH dose-dependently decreased BMD and bone strength in rats fed the low-protein diet. There was no significant effect of bGH on BMD in rats fed the normal protein diet within this short-term treatment period, however bone formation as detected by histomorphometry was improved in this group but not the low-protein group. Osteoclast surface was increased in the low-protein bGH-treated animals only. Changes in bone turnover markers were detectable under both normal and low-protein diets. Conclusion These results emphasize the major importance of dietary protein intake in the bone response to short-term GH administration, and highlight the need for further investigation into the effects of GH treatment in patients with reduced protein intake.

Correlations between biochemical markers of bone turnover and bone density responses in patients with glucocorticoid-induced osteoporosis treated with teriparatide or alendronate

The purpose of this post hoc analysis was to determine whether baseline concentrations or early changes in serum bone turnover markers were correlated with changes in bone mineral density (BMD) at 18 months in patients with glucocorticoid-induced osteoporosis (GIO) treated with teriparatide ( n = 80; 20 μg/day) or alendronate ( n = 77; 10 mg/day). Bone markers included type I collagen N-terminal propeptide (PINP), type I collagen C-terminal propeptide (PICP), bone alkaline phosphatase (bone ALP), and cross-linked C-telopeptide of type I collagen (Sβ-CTX). The relationship between baseline and early changes in markers and the 18-month changes in lumbar spine (LS) and femoral neck (FN) BMD was evaluated using Spearman correlation analysis. In the teriparatide group, increases in LS and FN BMD at 18 months were not significantly correlated with baseline marker concentrations (P > 0.05) but were correlated with the increases in PINP at 1 and 6 months ( P < 0.05). In the alendronate group, the increase in FN BMD at 18 months was positively correlated with baseline marker concentrations ( P < 0.05) and negatively correlated with change in PINP and Sβ-CTX at 1 and 6 months. In addition, in the alendronate group, the increase in LS BMD was negatively correlated with change in Sβ-CTX at 1 month ( P < 0.05). Increases in BMD at the spine and hip were independent of baseline bone turnover in the teriparatide group, while increases in hip BMD were dependent on baseline bone turnover in the alendronate group. With both therapies, early changes in some bone turnover markers were correlated with 18-month gains in BMD in patients with GIO.

Efficacy and safety of monthly ibandronate in men with low bone density

Introduction Monthly oral ibandronate is indicated for the prevention and treatment of osteoporosis in postmenopausal women. The STudy Researching Osteoporosis iN Guys (STRONG) investigated the efficacy and safety of 150-mg monthly oral ibandronate in men with primary, idiopathic, or hypogonadism-related low bone density. Methods STRONG was a 1-year, placebo-controlled, randomized (2 ibandronate: 1 placebo), double-blind study that enrolled ambulatory men aged ≥ 30 years with baseline femoral neck (FN) bone mineral density (BMD) T-scores ≤ − 2.0 and lumbar spine (LS) BMD T-scores ≤ − 1.0 or LS BMD T-scores ≤ − 2.0, FN BMD T-scores ≤ − 1.0, and BMD T-scores ≥ − 4.0 at any site assessed by dual-energy X-ray absorptiometry. The primary endpoint was mean percent change from baseline in LS BMD at 1 year (intent-to-treat [ITT] population). Secondary endpoints included mean BMD changes from baseline at the FN, total hip (TH), and trochanter (TR) and changes in bone turnover markers (BTMs), as measured by the bone resorption marker serum C-terminal telopeptide of type 1 collagen (sCTX) and the bone formation marker bone-specific alkaline phosphatase (BSAP). All men received twice daily calcium carbonate (1000 mg/day) and vitamin D (400 IU/day). Changes in BMD for treatment groups were compared using analysis of covariance with treatment, investigative site, and baseline testosterone as factors and baseline BMD as a covariate. Results The ITT population consisted of 132 men; 47 received placebo and 85 received monthly ibandronate. Men who received ibandronate achieved greater increases in LS BMD at 12 months than those who received placebo (3.5% vs. 0.9%, respectively; difference, 2.6; p < 0.001). The ibandronate group also achieved greater 12-month BMD increases than the placebo group, respectively, at the TH (1.8% vs. − 0.3%; difference, 2.1; p < 0.001), FN (1.2% vs. − 0.2%; difference, 1.4; p = 0.012), and TR (2.2% vs. 0.4%; difference, 1.7; p < 0.005). In men who completed the study and adhered to the protocol (per-protocol (PP) population), percent decreases in median sCTX and BSAP levels from baseline were also greater with ibandronate versus placebo ( p ≤ 0.001 for both comparisons). Overall, monthly ibandronate was well tolerated. Conclusions In men with low BMD, 1 year of treatment with oral once-monthly 150-mg ibandronate significantly increased BMD at the LS and hip (TH, TR, and FN), significantly reduced BTM levels in the PP population, and was generally well tolerated.

Comparison in bone turnover markers during early healing of femoral neck fracture and trochanteric fracture in elderly patients

Healing of fractures is different for each bone and bone turnover markers may reflect the fracture healing process. The purpose of this study was to determine the characteristic changes in bone turnover markers during the fracture healing process. The subjects were consecutive patients with femoral neck or trochanteric fracture who underwent surgery and achieved bone union. There were a total of 39 patients, including 33 women and 6 men. There were 18 patients (16 women and 2 men) with femoral neck fracture and 21 patients (17 women and 4 men) with trochanteric fracture. Serum bone-specific alkaline phosphatase (BAP) was measured as a bone formation marker. Urine and serum levels of N-terminal telopeptide of type I collagen (NTX), as well as urine levels of C-terminal telopeptide of type I collagen (CTX) and deoxypyridinoline (DPD), were measured as markers of bone resorption. All bone turnover markers showed similar changes in patients with either type of fracture, but significantly higher levels of both bone formation and resorption markers were observed in trochanteric fracture patients than in neck fracture patients. BAP showed similar levels at one week after surgery and then increased. Bone resorption markers were increased after surgery in patients with either fracture. The markers reached their peak values at three weeks (BAP and urinary NTX), five weeks (serum NTX and DPD), and 2–3 weeks (CTX) after surgery. The increase in bone turnover markers after hip fracture surgery and the subsequent decrease may reflect increased bone formation and remodeling during the healing process. Both fractures had a similar bone turnover marker profile, but the extent of the changes differed between femoral neck and trochanteric fractures.

The Effect of Yoga on Markers of Bone Turnover in Osteopenic Women: a Pilot Study

Weight-bearing exercise is recommended to improve bone density. Hatha Yoga is a popular form of weight-bearing exercise that includes physical postures, stretching, breathing, and relaxation. We hypothesized that Hatha Yoga would have beneficial effects on bone turnover markers. We conducted a small feasibility pilot study with a prospective, pre-post design comparing markers of bone turnover before and after Yoga training in sedentary osteopenic postmenopausal women. Markers of bone formation were measured with serum bone-specific alkaline phosphatase (BAP). Measures of bone resorption were measured with urinary type I collagen cross-linked N-telopeptide (uNTX). Seven participants completed a 12-week series of one hour per week Yoga classes, in addition to home Yoga practice. We analyzed the correlation between time spent on Yoga and time spent on other weight-bearing exercise and change in bone turnover markers. The amount of Yoga practice was significantly correlated with BAP levels (r = 0.68, p = 0.09). A weaker, non-significant correlation was found between the amount of Yoga practice and uNTX levels (r = -.54, p = .21). Compared to Yoga, other physical activities were less correlated with BAP and uNTX levels. Yoga may have beneficial effects on bone turnover in osteopenic postmenopausal women.

Effects of Yearly Zoledronic Acid 5 mg on Bone Turnover Markers and Relation of PINP With Fracture Reduction in Postmenopausal Women With Osteoporosis

In patients with osteoporosis treated with antiresorptive agents, reduction in bone turnover explains much of the observed fracture risk reduction. Lower levels of bone turnover markers (BTMs) appear to be associated with a lower risk of fracture in bisphosphonate-treated patients. BTMs were measured in a subset of subjects in the HORIZON Pivotal Fracture Trial. Annual infusions of zoledronic acid 5 mg significantly reduced BTMs: median decrease of 50% for beta-C-terminal telopeptides of type 1 collagen (beta-CTX), 30% for bone alkaline phosphatase (ALP), and 56% for procollagen type 1 amino-terminal propeptide (PINP). The mean level of BTMs decreased in treated patients but remained within the premenopausal range before the next injection. The percentage of zoledronic acid-treated patients with values below the premenopausal reference range at all time points was 1.7%, 17.8%, and 19% for bone ALP, CTX, and PINP, respectively. The third injection of zoledronic acid resulted in 60% reduction of beta-CTX within 9-11 days, followed by a gradual increase, indicating the persistence of osteoclastic bone resorption. The association between changes in BTMs and fracture incidence was assessed in 1132 patients who had PINP measurements at baseline and 1 yr. There was no association between low PINP levels at 1 yr and increased fracture incidence. In summary, (1) annual injections of zoledronic acid reduced BTMs in the premenopausal range, with a significant response persisting after the third infusion; and (2) low levels of PINP were not associated with increased fracture risk.

Diabetes and skeletal health

Osteoporosis and diabetes affect a large proportion of the elderly population. The prevalence of diabetes and osteoporosis is increasing. Compared with individuals without diabetes, both men and women with diabetes have a higher risk of fractures, particularly at the hip, with consequent significant morbidity and mortality. Type 1 diabetes is associated with decreased bone mass and although bone mass data for Type 2 diabetes may or may not be decreased, there is evidence of altered bone quality in diabetes. The mechanisms involved include effects of insulin, insulin-like growth factor 1, cytokines, advanced glycation end products, and altered calcium homeostasis. In addition, a drug-induced increase in the incidence of fractures has been noted with the use of thiazolidinediones (TZDs). TZDs improve insulin sensitivity and have multitude other beneficial effects. Osteoblasts and adipocytes are derived from a common multipotential mesenchymal stem cell progenitor, with activation of peroxisome proliferator-activated receptor γ2 by both currently available TZDs (i.e. rosiglitazone and pioglitazone) stimulating adipogenesis and inhibiting osteoblastogenesis. The use of both rosiglitazone and pioglitazone is associated with an increased fracture risk, with changes in bone turnover markers and decreased bone mineral density.

Rapid and robust response of biochemical markers of bone formation to teriparatide therapy

Teriparatide, a parathyroid hormone analogue, is a potent anabolic treatment for postmenopausal osteoporosis. Studies have shown that teriparatide induces large increases in biochemical markers of bone formation after 1 month of therapy followed by a delayed increase in bone resorption markers. The aims of this study were to (1) describe changes in bone turnover markers during 28 days of treatment with teriparatide; (2) identify the earliest time point by which most subjects showed a biochemical response to teriparatide; (3) identify potential biomarkers of positive bone response; (4) describe changes in bone turnover markers 4 weeks after stopping teriparatide. We recruited 15 osteopenic postmenopausal women, ages 55–69 (mean 62) years. All received 20 μg teriparatide subcutaneously for 28 days. Serum levels of the bone formation markers type I collagen N-terminal propeptide (PINP), type I collagen C-terminal propeptide (PICP), osteocalcin (OC), bone alkaline phosphatase (bone ALP), and the bone resorption markers crosslinked C-telopeptide of type I collagen (Sβ-CTX), crosslinked N-telopeptide of type I collagen (S-NTX) and tartrate-resistant acid phosphatase type 5b (TRACP5b) were measured on 11 occasions: three times before dosing (baseline) and on days 3, 7, 10, 14, 19, 24 and 28 and at day 56 (i.e., 28 days after stopping teriparatide ). During the first 2 days of teriparatide treatment, PINP levels increased rapidly, by 8.2% (90% confidence interval (CI) 6.9%, 9.5%) and continued to increase until the end of treatment to 110.8%. PICP and OC showed a similar, but less pronounced, pattern. All three markers increased by at least 75% at day 28. A small, transient decrease in bone resorption markers occurred over the same period. Following cessation of treatment, concentrations of bone formation markers decreased to within 20% of baseline values by day 56. In conclusion, the bone formation markers PINP, PICP and OC show a rapid and robust increase in response to teriparatide, which is noticeable during the first week of therapy. PINP is the most responsive marker. These findings have important implications for monitoring patients treated with teriparatide and may also inform the design of studies of new anabolic agents for osteoporosis.

Biochemical markers of bone turnover. New aspect. Changes in bone turnover markers during fracture healing

Fracture may influence the serum and urine levels of bone turnover markers, however, the changes in bone markers seem to be not constant. The magnitude of change may be dependent on the size of the fractured bone, the amount of bone involved, and difference in bone markers. In patients with hip fracture, there was early increase in bone resorption markers within 2 weeks after fracture, and resorption markers started to decrease 2-3 months after fracture and stabilized close to prefracture level by about 6 months after fracture. Bone formation markers peaked later than bone resorption markers and remained elevated up to 1 year after fracture. This elevation in bone turnover markers reflects the repair process after fracture, and also immobilization following fracture, bone loss close to the fracture, and post-traumatic systemic reactions contribute to the accelerated bone formation and resorption.