Reference intervals of bone turnover markers determined by using their curve-fitting valley for adult females in China

Summary

The reference values for bone turnover markers (BTMs) have a significant role in the diagnosis, monitoring, and treatment of metabolic bone disease. This study proposes that the peak value of bone mineral density and the trough value for the BTM curve can be used to determine the reference range of BTM.

Introduction

The aim of this study is to determine the reference intervals of BTMs for adult females in China with an attempt to reference the peak bone mineral density (BMD) with the corresponding BTM valley.

Methods

This study included 546 premenopausal and 394 postmenopausal women. The levels of several BTMs were determined, and the BMD was measured using a dual-energy X-ray absorptiometry.

Results

The BTMs of postmenopausal women were 17–96 % higher than premenopausal women. The change of BTM with age presented an optimal goodness-of-fit according to the cubic regression model (R ²?=?0.074–0.346, all P?=?0.000). All kinds of BTM levels were positively correlated with age in premenopausal women aged 27–56 years old (r?=?0.167–0.502, P?=?0.023–0.000). Except for uCTX, the BTM reference value determined using a curve-fitting valley was significantly lower than the reference values for premenopausal women. The BTM reference values determined in this study were also significantly different from the reference values given by the manufacturers of the reagents used.

Conclusions

This study found that the changes of level with age of BTMs in Chinese women present an optimal goodness-of-fit according to the cubic regression model. The fitting valley corresponds to the BMD fitting peak and may possibly be an effective means of determining the BTM reference intervals.     

Association between coronary artery calcification using low-dose MDCT coronary angiography and bone mineral density in middle-aged men and women

Summary

Six hundred sixty-one participants who had at least one cardiac risk factor but were without known coronary heart disease underwent low-dose multidetector computed tomography coronary angiography (MDCT-CA) and dual-energy X-ray absorptiometry. The association between presence of subclinical coronary calcified plaque and low bone mineral density for the middle-aged individual was not significant after multivariate adjustment.

Introduction

Results of previous clinical studies assessing the relationship between osteoporosis and coronary calcification are inconsistent. This study aimed to evaluate the association between subclinical coronary calcification and osteoporosis in middle-aged men, premenopausal women, and postmenopausal women by using low-dose MDCT-CA and bone mineral density (BMD).

Methods

This study enrolled 661 participants with at least one cardiac risk factor but without known coronary artery disease (CAD). All subjects underwent low-dose MDCT-CA and dual-energy X-ray absorptiometry on the same day.

Results

The mean age was 52.2 years for men, 44.8 years for premenopausal women, and 59.1 years for postmenopausal women. The prevalence of calcified plaques between men with normal BMD and low BMD at lumbar spine were significantly different (P?=?0.042). The prevalence of mixed plaque and calcified plaque between pre- and postmenopausal women with normal BMD and low BMD at lumbar spine and femoral neck were not significantly different (P?>?0.05). Possible association between lumbar spine, femoral neck, and total proximal femur BMD and the presence of CAP was evaluated for men, premenopausal women, and postmenopausal women using multivariate logistic regression analysis: results were not significant (P?>?0.05).

Conclusion

Our study demonstrates that the association between the presence of subclinical coronary calcification and low BMD among middle-aged men and women was not significant after controlling for age and other risk factors for CAD and osteoporosis.     

Effect of once-yearly zoledronic acid on the spine and hip as measured by quantitative computed tomography: results of the HORIZON Pivotal Fracture Trial

Summary

Changes in bone mineral density and bone strength following treatment with zoledronic acid (ZOL) were measured by quantitative computed analysis (QCT) or dual-energy X-ray absorptiometry (DXA). ZOL treatment increased spine and hip BMD vs placebo, assessed by QCT and DXA. Changes in trabecular bone resulted in increased bone strength.

Introduction

To investigate bone mineral density (BMD) changes in trabecular and cortical bone, estimated by quantitative computed analysis (QCT) or dual-energy X-ray absorptiometry (DXA), and whether zoledronic acid 5 mg (ZOL) affects bone strength.

Methods

In 233 women from a randomized, controlled trial of once-yearly ZOL, lumbar spine, total hip, femoral neck, and trochanter were assessed by DXA and QCT (baseline, Month 36). Mean percentage changes from baseline and between-treatment differences (ZOL vs placebo, t-test) were evaluated.

Results

Mean between-treatment differences for lumbar spine BMD were significant by DXA (7.0%, p?<?0.01) and QCT (5.7%, p?<?0.0001). Between-treatment differences were significant for trabecular spine (p?=?0.0017) [non-parametric test], trabecular trochanter (10.7%, p?<?0.0001), total hip (10.8%, p?<?0.0001), and compressive strength indices at femoral neck (8.6%, p?=?0.0001), and trochanter (14.1%, p?<?0.0001).

Conclusions

Once-yearly ZOL increased hip and spine BMD vs placebo, assessed by QCT vs DXA. Changes in trabecular bone resulted in increased indices of compressive strength.     

Zoledronic acid enhances bone-implant osseointegration more than alendronate and strontium ranelate in ovariectomized rats

Summary

This study was designed to compare the effects of alendronate (ALN), strontium ranelate (SR), and zoledronic acid (ZOL) on bone-implant osseointegration in ovariectomized rats. Histological examination and biomechanical tests show that ZOL, ALN, and SR enhance bone-implant osseointegration; ALN and SR have similar effects, while ZOL enhances bone-implant osseointegration more than ALN and SR

Introduction

This study aims to compare the effects of ALN, SR, and ZOL on bone-implant osseointegration in ovariectomized rats.

Methods

Sixty female Sprague–Dawley rats were included in this study. Of them, 48 rats were ovariectomized (OVX) and assigned to four groups: OVX (OVX?+?Veh), ALN (OVX?+?ALN), SR (OVX?+?SR), and ZOL (OVX?+?ZOL). And another 12 rats were sham-operated as a control group (Sham). Four weeks after ovariectomy, HA-coated titanium implants were inserted into the tibias bilaterally in all rats. Then the rats in groups ALN, SR, and ZOL were systemically administrated with alendronate (7 mg/kg/week, orally), strontium ranelate (500 mg/kg/day, orally), or a single injection of zoledronic acid (0.1 mg/kg, iv), respectively. Twelve weeks after implantation, all rats were sacrificed to get the femurs and tibias. Histological examination and biomechanical tests were used to evaluate bone-implant osseointegration in all groups.

Results

ALN, SR, and ZOL significantly increased distal femoral BMD when compared with group OVX; ZOL increased BMD significantly more than ALN and SR (P?<?0.05). Significant increase of bone-to-implant contact and peri-implant bone fraction were observed in groups ALN, SR, and ZOL when compared with group OVX (P?<?0.05). Groups ALN and SR were inferior to groups ZOL and Sham (P?<?0.05) in bone-to-implant contact and peri-implant bone fraction. Similar results were found in biomechanical testing (max pushout force).

Conclusions

In rats losing bone rapidly after ovariectomy, systemic administration of ZOL, ALN, and SR causes better bone-implant osseointegration when compared to OVX; ALN and SR have similar positive effects on osseointegration, while ZOL, that was given in a dose with more positive BMD effect than that of ALN or SR, causes better osseointegration than either ALN or SR.     

Relationship of thoracic kyphosis and lumbar lordosis to bone mineral density in women

Summary

The relationship between spinal curvature and bone mineral density (BMD) in women was examined. Significant relationships were observed between spinal curvature and BMD in both pre- and postmenopausal women. Excessive spinal curvature may be associated with low bone mass in premenopausal women.

Introduction

The purpose of this study was to examine the associations between spinal measurements of thoracic and lumbar curvatures and bone mineral density in pre- and postmenopausal women.

Methods

The data for this study were obtained from the Texas Woman’s University Pioneer Project. Female participants (n?=?242; premenopausal n?=?104, postmenopausal n?=?138) between the ages of 18 and 60 years were evaluated on multiple health measures. Thoracic and lumbar curvatures were measured with a 24-in. (60 cm) flexicurve. Bone mineral density was assessed via dual-energy X-ray absorptiometry (Lunar DPX IQ, version 4.6e). Pearson correlations and logistic regression analysis were used to examine the associations between the obtained spinal curvature measurements and bone mineral density. Significance was set at p?<?.05.

Results

Significant correlations were observed for the femoral neck and lumbar spine bone mineral density with thoracic and lumbar curve in premenopausal women (r?=??.344 to???.525; p?<?.001). Slightly weaker, but significant, correlations were observed for femoral neck and lumbar spine in relation to thoracic and lumbar curve in postmenopausal women (r?=??.288 to ?.397; p?<?.01). Premenopausal women with thoracic curvature greater than 4 cm had a greater risk of having low bone mass compared to premenopausal women with less than 4 cm of curvature (odds ratio?=?3.982, 95 % CI?=?1.206, 13.144).

Conclusions

The observed negative relationship suggests that as either thoracic or lumbar curvature increases, the regional bone mineral density decreases in both pre- and postmenopausal women.     

High serum pentosidine but not esRAGE is associated with prevalent fractures in type 1 diabetes independent of bone mineral density and glycaemic control

Summary

Fracture risk in type 1 diabetes (T1D) is supposed to be underestimated by bone mineral density (BMD). Individuals with T1D had more prevalent fractures in a cross-sectional study. Serum levels of pentosidine, an advanced glycation end product, and poor glycaemic control were associated with prevalent fractures independent of BMD.

Introduction

Type 1 diabetes (T1D) is associated with increased fracture risk. Bone mineral density (BMD) underestimates the risk of fractures in some individuals. The accumulation of advanced glycation end products (AGEs) impairs bone matrix and reduces bone strength.

Methods

In a cross-sectional study, 128 men and premenopausal women with T1D were evaluated. We compared traditional risk factors for fractures, BMD, parameters of bone metabolism and AGEs in individuals with and without prevalent fractures. An independent association of serum AGE levels with prevalent fractures was investigated.

Results

Individuals with prevalent fractures exhibited a longer duration of T1D, higher HbA1c and more diabetic-related complications. BMD at the femoral neck (z-score ?0.76?±?0.94 vs. ?0.23?±?1.02; p?=?0.031) and total hip (z-score ?0.54?±?0.93 vs. 0.11?±?1.11; p?=?0.017) was lower in those with prevalent fractures. Individuals with fractures had higher pentosidine levels (164.1?±?53.6 vs. 133.2?±?40.4; p?=?0.002). The levels of N-ε-(carboxymethyl)-lysine (CML) and endogenous secretory receptor for AGEs (esRAGE) did not significantly differ. Multivariate logistic regression analysis adjusted for age, BMI, family history of fractures, smoking, vitamin D deficiency, BMD at lumbar spine, femoral neck and total hip identified pentosidine levels and HbA1c as independent factors associated with prevalent fractures (odds ratio 1.02, 95 % CI 1.00–1.03/pmol/ml increase of pentosidine; p?=?0.008 and odds ratio 1.93, 95 % CI 1.16–3.20 per percentage increase of HbA1c; p?=?0.011).

Conclusions

The pentosidine levels but not BMD are independently associated with prevalent fractures. Impaired bone quality in T1D may result from increased AGE formation.     

Changes in Bone Mineral Density After Sleeve Gastrectomy or Gastric Bypass: Relationships with Variations in Vitamin D,Ghrelin, and Adiponectin Levels

Background

A major long-term concern after gastric bypass (GBP) is the risk of osteoporosis; however, little is known about this complication in patients undergoing sleeve gastrectomy (SG).

Objective

To evaluate changes in bone mineral density (BMD) after GBP and SG, and its relationship with changes in vitamin D, parathyroid hormone (PTH), ghrelin, and adiponectin.

Methods

Twenty-three women undergoing GBP (BMI 42.0?±?4.2 kg/m²; 37.3?±?8.1 years) and 20 undergoing SG (BMI 37.3?±?3.2 kg/m²; 34.2?±?10.2 years) were studied before and 6 and 12 months after surgery. BMD was measured by dual-energy X-ray absorptiometry. Plasma PTH, 25-hydroxyvitamin D (25-OHD), ghrelin, and adiponectin concentrations were determined. Food as well as calcium and vitamin D supplement intake was recorded.

Results

Excess weight loss (mean?±?SE), adjusted by baseline excess weight, was 79.1±3.8 % and 74.9?±?4.1 % 1 year after GBP and SG, respectively (p?=?0.481). Significant reduction in BMD for total body (TB), lumbar spine (LS), and femoral neck (FN) was observed after GBP. In the SG group, reduction in BMD was significant only for TB. Adjusted by baseline BMD, the difference between change in BMD for GBP vs. SG was not significant for TB, LS, or FN. Percent reduction in ghrelin concentration was a main factor related to total BMD loss (GBP group) and LS BMD loss (GBP and SG groups).

Conclusions

One year after gastric bypass, bone mineral density was significantly affected, mainly at the femoral neck. Decreases in bone mineral density were more dramatic among patients who had greater baseline BMD and greater reduction in ghrelin concentrations.     

Physical activity throughout adolescence and bone mineral density in early adulthood: the 1993 Pelotas (Brazil) Birth Cohort Study

Summary

Association between three physical activity (PA) measurements throughout adolescence and bone density at 18 years of age was investigated. PA was associated with both lumbar spine and femoral neck bone mineral density (BMD) in early adulthood independent of type of PA used in the analysis. The results were more consistent in boys.

Introduction

This study amis to evaluate if PA during adolescence could influence BMD later in life.

Methods

A population-based birth cohort study was carried out. PA was assessed at 11 and 15 years of age by questionnaire and included sports performed while BMD (lumbar spine and femoral neck) was measured by dual-energy X-ray absorptiometry at 18 years. A peak strain score was generated based on ground reaction forces of different PA. PA was measured as peak strain score, peak strain score multiplied by minutes/week and minutes/week. Unadjusted and adjusted analyses were performed using linear regression.

Results

Overall, 3,811 adolescents were studied (1,866 boys and 1,945 girls). The peak strain score at 11 and 15 years was associated with lumbar and femoral neck BMD at 18 years in boys. Among girls, high-impact PA at 11 years was positively associated with lumbar and femoral BMD (p?=?0.01; p?<?0.001). After adjusted analysis, weekly minutes of PA at 11 years were not associated with lumbar spine but were associated with femoral neck BMD (p?<?0.001); at 15 years, weekly minutes of PA were positively associated with BMD at both sites. Regardless of PA status at 11 years of age, attaining the recommendations of PA (300 min/week) at 15 years appears to be important for BMD at 18 years in both sites in boys and girls. The results Appeared to be more consistent in boys.

Conclusions

PA during adolescence was positively associated with both lumbar spine and femoral neck BMD in early adulthood independent of type of PA used in the analysis.     

Effects of cinacalcet on bone mineral density and bone markers in hemodialysis patients with secondary hyperparathyroidism

Background

Cinacalcet markedly reduces the serum intact parathyroid hormone (PTH) level of hemodialysis (HD) patients with secondary hyperparathyroidism. Parathyroidectomy also reduces the serum intact PTH level of HD patients and it increases their bone mineral density (BMD). However, there is little information about the effect of cinacalcet on BMD or on the associations between bone markers and BMD in HD patients.

Methods

We performed a 1-year cohort study of 25 HD patients who had a serum intact PTH level above 300 pg/ml during treatment by conventional therapies, such as with active vitamin D, and cinacalcet was prescribed for 14 of them. BMD of the femoral neck and the serum levels of two circulating bone markers, alkaline phosphatase (ALP) and bone-specific alkaline phosphatase (BSAP), were measured before and after treatment. The other 11 HD patients without cinacalcet treatment were defined as control group.

Results

BMD significantly increased by 7.3 % during the 1 year of treatment in the cinacalcet group and decreased by 6.2 % during the same period in the control group, and cinacalcet therapy was independently associated with the changes in BMD after multiple regression analysis that included intact PTH (β = 7.57, P < 0.01). In the cinacalcet group, the serum ALP levels (R ² = 0.315, P < 0.05) and BSAP levels (R ² = 0.682, P < 0.01) levels were significantly negatively correlated with the changes in BMD, but the serum intact PTH levels were not significantly associated with the changes in BMD (R ² = 0.011, P = 0.72).

Conclusions

One year of treatment with cinacalcet increased the BMD of the femoral neck in the HD cohort, especially in the patients who had higher serum ALP and BSAP levels at baseline.     

Impact + resistance training improves bone health and body composition in prematurely menopausal breast cancer survivors: a randomized controlled trial

Summary

Our randomized controlled trial in prematurely menopausal breast cancer survivors showed that impact + resistance training prevented increases in percentage of body fat compared with controls and also improved BMD at the hip and prevented BMD loss at the spine among exercise-trained women who were menopausal for >1 year.

Introduction

Cancer treatment-related menopause worsens bone health and body composition in breast cancer survivors (BCS). We investigated whether impact + resistance training could improve bone mineral density (BMD), reduce bone turnover, build muscle, and decrease fat mass in BCS with premature menopause.

Methods

We conducted a randomized controlled trial in 71 BCS (mean age, 46.5 years) within 5 years of treatment-related menopause. Women were randomly assigned to one of two groups: (1) impact + resistance training (prevent osteoporosis with impact + resistance (POWIR)) or (2) exercise placebo (FLEX) 3×/week for 1 year. Outcomes were hip and spine BMD (in grams per square centimeter) and body composition (percent body fat (%BF) and lean and fat mass (in kilograms)) by DXA and bone turnover markers (serum osteocalcin (in nanograms per milliliter) and urinary deoxypryrodinoline (in nanomoles per milliliter).

Results

There were no significant group × time interactions for bone outcomes when using an intent-to-treat approach on the full sample. In analyses restricted to BCS who were menopausal for ≥1 year, POWIR increased BMD at the hip and slowed BMD loss at the spine compared with FLEX (femoral neck—POWIR, 0.004?±?0.093 g/cm² vs. FLEX, ?0.010?±?0.089 g/cm²; p?<?0.01; spine—POWIR, ?0.003?±?0.114 g/cm² vs. FLEX, ?0.020?±?0.110 g/cm²; p?=?0.03). POWIR prevented increases in %BF (POWIR, 0.01 % vs. FLEX, 1.3 %; p?<?0.04). Women with attendance to POWIR at ≥64 % had better improvements in %BF than women attending less often (p?<?0.03).

Conclusion

Impact + resistance training may effectively combat bone loss and worsening body composition from premature menopause in BCS.     

BMD improvements after operation for primary hyperparathyroidism

Purpose

This study aims to quantify bone mineral density (BMD) changes following surgery in patients with primary hyperparathyroidism (PHPT) and to assess their relationship with clinical and biochemical variables.

Methods

A historic cohort of 236 PHPT patients with DXA scans pre- and 1-year postoperatively, clinical data, and biochemical data was analyzed.

Results

The mean age was 60 years (range 19–86) and 81 % of the patients were women. A significant postoperative 2.6 % (95 % CI, 2.1; 3.1) increase in lumbar spine BMD was seen. The increase in BMD was positively associated with preoperative plasma PTH (p?=?0.002), Ca²⁺ (p?<?0.001), and alkaline phosphatase (p?=?0.014). Hip BMD increased 1.5 % (1.1; 1.9). The increase in BMD was positively associated with preoperative plasma PTH (p?=?0.005) and Ca²⁺ (p?<?0.001) and inversely associated with plasma creatinine (p?=?0.004) and age (p?=?0.018). Total forearm BMD did not change significantly (?0.2 % (?0.5; 0.1)). An increase in forearm BMD was seen in 38 % of all patients, and the changes were positively associated with plasma PTH (p?<?0.001) and Ca²⁺ (p?=?0.009). In all 91 patients with mild PHPT (plasma Ca²⁺?<?1.45 mmol/l), there was a significant postoperative increase in spine BMD (1.9 % (1.2; 2.7)) and in hip BMD (1.0 % (0.4; 1.6)), but not in the forearm BMD (?0.3 % (?0.7; 0.2)). The postoperative BMD gain was higher in the hip and forearm in patients operated for adenomas compared with patients treated for hyperplasia.

Conclusions

We found significant postoperative BMD improvements both at the hip and the spine. BMD improvements were also significant in mild cases. At all scan sites, there were positive associations between preoperative plasma PTH levels and postoperative BMD increases. The measured BMD changes may mainly be due to a decrease in PTH-induced bone turnover with refilling of the remodeling space.     

Association between hypertension and fragility fracture: a longitudinal study

Summary

Hypertension is an independent risk factor for osteoporosis and osteoporotic fracture in postmenopausal women.

Introduction

Although hypertension has been suggested to be associated with increased fracture risk, it is not clear whether the association is independent of bone mineral density (BMD). The present study sought to examine the interrelationships between hypertension, BMD, and fracture risk.

Methods

The study included 1,032 men and 1,701 women aged 50 years and older who were participants in the Dubbo Osteoporosis Epidemiology Study. BMD at the femoral neck and lumbar spine was measured by dual energy X-ray absorptiometry (GE-LUNAR Corp., Madison, WI, USA). The presence of hypertension was ascertained by direct interview and verification through clinical history. The incidence of fragility fractures was ascertained by X-ray report during the follow-up period (1989–2008). The Cox proportional hazards model was used to assess the association between hypertension and fracture risk.

Results

Women with hypertension had lower BMD at the femoral neck (0.79 versus 0.82 g/cm², P?=?0.02) than those without the disease. After adjusting for BMD and covariates, hypertension was an independent risk factor for fragility fracture [hazard ratio (HR), 1.49; 95 % CI, 1.13–1.96]. In men, hypertension was associated with higher femoral neck BMD (0.94 versus 0.92 g/cm², P?=?0.02), but the association between hypertension and fracture risk did not reach statistical significance.

Conclusion

Hypertension is associated with increased fracture risk in women, and the association is independent of BMD.     

Predictors of low bone mineral density of the stroke-affected hip among ambulatory individuals with chronic stroke

Summary

Risk of hip fracture is greater poststroke than in an age-matched healthy population, in part because of declining hip BMD. We found that individuals may be at risk of loss of hip BMD from muscle atrophy, asymmetrical gait, and poor affected-side ankle dorsiflexor strength. These impairments may be targeted during rehabilitation.

Introduction

This study aimed to determine predictors of low hip BMD on the stroke-affected side in people living in the community.

Methods

Forty-three participants (female; 27.9 %), mean age 62.4?±?13.5 and 17.9?±?32.8 months, poststroke with motor impairments underwent dual energy X-ray absorptiometry scans. Gait characteristics, isometric strength, body composition, and fasting plasma lipids were measured.

Results

At entry, 34.9 % (15/43) of the participants had low total hip BMD on the stroke-affected side. Of those with low BMD, 93.3 % (14/15) had a step length symmetry ratio >1, indicating greater reliance on the non-paretic leg for weight bearing. Logistic regression analysis revealed that lower affected-side ankle dorsiflexor strength (ß?=?0.700, p?=?0.02), lower total body fat-free mass index (ß?=?0.437, p?=?0.02), and greater step length symmetry ratio during walking (ß?=?1.135?×?10³, p?=?0.03) were predictors of low hip BMD.

Conclusion

Low BMD of the stroke-affected side hip is prevalent in over a third of individuals with lower limb motor impairments. These individuals may be at particular risk of accelerated loss of BMD at the hip from asymmetrical gait pattern and poor affected-side ankle dorsiflexor strength. These impairments are intervention targets that may be addressed during rehabilitation which includes resistance training and addresses gait impairments.     

Comparative effects of teriparatide and ibandronate on spine bone mineral density (BMD) and microarchitecture (TBS) in postmenopausal women with osteoporosis: a 2-year open-label study

Summary

Treatment effects over 2 years of teriparatide vs. ibandronate in postmenopausal women with osteoporosis were compared using lumbar spine bone mineral density (BMD) and trabecular bone score (TBS). Teriparatide induced larger increases in BMD and TBS compared to ibandronate, suggesting a more pronounced effect on bone microarchitecture of the bone anabolic drug.

Introduction

The trabecular bone score (TBS) is an index of bone microarchitecture, independent of bone mineral density (BMD), calculated from anteroposterior spine dual X-ray absorptiometry (DXA) scans. The potential role of TBS for monitoring treatment response with bone-active substances is not established. The aim of this study was to compare the effects of recombinant human 1–34 parathyroid hormone (teriparatide) and the bisphosphonate ibandronate (IBN), on lumbar spine (LS) BMD and TBS in postmenopausal women with osteoporosis.

Methods

Two patient groups with matched age, body mass index (BMI), and baseline LS BMD, treated with either daily subcutaneous teriparatide (N?=?65) or quarterly intravenous IBN (N?=?122) during 2 years and with available LS BMD measurements at baseline and 2 years after treatment initiation were compared.

Results

Baseline characteristics (overall mean ± SD) were similar between groups in terms of age 67.9?±?7.4 years, body mass index 23.8?±?3.8 kg/m², BMD L1–L4 0.741?±?0.100 g/cm², and TBS 1.208?±?0.100. Over 24 months, teriparatide induced a significantly larger increase in LS BMD and TBS than IBN (+7.6 %?±?6.3 vs. +2.9 %?±?3.3 and +4.3 %?±?6.6 vs. +0.3 %?±?4.1, respectively; P?<?0.0001 for both). LS BMD and TBS were only weakly correlated at baseline (r ²?=?0.04) with no correlation between the changes in BMD and TBS over 24 months.

Conclusions

In postmenopausal women with osteoporosis, a 2-year treatment with teriparatide led to a significantly larger increase in LS BMD and TBS than IBN, suggesting that teriparatide had more pronounced effects on bone microarchitecture than IBN.     

Changes in Bone Mineral Density in Women Following 1-Year Gastric Bypass Surgery

Background

Roux-en-Y gastric bypass (RYGB) surgery is the gold standard surgical treatment for obesity. However, unintended nutritional deficiencies following this surgery are common, including changes in bone metabolism. We assessed changes in bone mineral density (BMD), nutritional compounds, and bone resorption markers before and 1?year following RYGB surgery.

Methods

Our study included 22 female patients with class II/III obesity. A clinical questionnaire, a 24-h recall, blood and urine samples, and dual-energy X-ray absorptiometry were provided.

Results

Mean age was 37.2?±?9.6?years; 86?% were Caucasian and 77.2?% were premenopausal. Mean preoperative body mass index was 44.4?±?5.0 and 27.5?±?4.5?kg/m² at 1-year follow-up (p?p?=?0.327]. Serum N-telopeptide (16.3?±?3.4 vs. 38.2?±?7.0 nM BCE, p?p?=?0.026) increased after RYGB surgery, reflecting bone resorption. BMD decreased after RYGB surgery in the lumbar spine (1.13?±?0.11 vs. 1.04?±?0.09?g/cm², p?=?0.001), femoral neck (1.03?±?0.15 vs. 0.94?±?0.16?g/cm², p?=?0.001), and total femur (1.07?±?0.11 vs. 0.97?±?0.15?g/cm², p?=?0.003).

Conclusions

Decreased BMD in the lumbar spine, femoral neck, and total femur is detectable in women 1?year after RYGB surgery. Calcium malabsorption, caused by vitamin D deficiency and increased bone resorption, is partially responsible for these outcomes and should be targeted in future clinical trials.     

The relationship between pulmonary function and bone mineral density in healthy nonsmoking women: the Korean National Health and Nutrition Examination Survey (KNHANES) 2010

Summary

The aim of this study was to examine the association between pulmonary function and bone mineral density (BMD) in subjects who had never smoked. Pulmonary function was associated with BMD in premenopausal, but not postmenopausal, women.

Introduction

It has been reported that low bone mass is common in patients with pulmonary disorders such as chronic obstructive pulmonary disease. However, in healthy nonsmoking women, the relationship between bone mass and pulmonary function has yet to be clarified. The object of this study was to determine whether pulmonary function is related to BMD in healthy nonsmoking women based on menopausal status.

Methods

This study was a cross-sectional study based on data obtained from the Korean National Health and Nutrition Examination Survey (KNHANES), a nationwide representative survey conducted by the Korean Ministry of Health and Welfare in 2010. This study included 456 subjects who had never smoked and analyzed data concerning pulmonary function and BMD.

Results

Functional vital capacity (FVC) and forced expiratory volume in 1 s (FEV1) were correlated with BMD at lumbar spine, femur neck (FN), and total hip in premenopausal women (p = 0.030, p = 0.003, p = 0.019, respectively, for FVC; p = 0.015, p = 0.006, p = 0.059, respectively, for FEV₁). However, FVC and FEV₁ were only correlated with BMD at FN in postmenopausal women (p = 0.003 for FVC; p = 0.006 for FEV₁). Body mass index (BMI), FVC, and FEV₁ were significantly related with BMD at FN, even after adjusting for age and other confounding factors (β = 0.334, p < 0.001; β = 0.145, p = 0.017; and β = 0.129, p = 0.037, respectively) in premenopausal women. However, only age and BMI were correlated with BMD at FN (β = ?0.268, p = 0.001 and β = 0.384, p > 0.001) in postmenopausal women after adjusting for confounding factors.

Conclusions

Pulmonary function, including FVC and FEV₁ are associated with BMD at FN in healthy nonsmoking premenopausal women but not in postmenopausal women.     

Cold-activated brown adipose tissue is an independent predictor of higher bone mineral density in women

Summary

In animals, defective brown adipogenesis leads to bone loss. Whether brown adipose tissue (BAT) mass relates to bone mineral density (BMD) in humans is unclear. We determined the relationship between BAT mass and BMD by cold-stimulated positron-emission tomography (PET) and dual-energy X-ray absorptiometry (DXA) in healthy volunteers. Higher BAT mass was associated with higher BMD in healthy women, but not in men, independent of age and body composition.

Introduction

Contrary to the traditional belief that BAT is present only in infants, recent studies revealed significant depots of BAT present in adult humans. In animals, defective brown adipogenesis leads to bone loss. While white adipose tissue mass is a known determinant of BMD in humans, the relationship between BAT and BMD in humans is unclear. We thus examined the relationship between BAT and BMD in healthy adults.

Methods

BAT volume (ml) and activity (standard uptake value) were determined by ¹⁸F-fluorodeoxyglucose PET after overnight mild cold exposure at 19 °C, and BMD was determined by DXA.

Results

Among 24 healthy adults (age 28?±?1 years, F?=?10), BAT volumes were 82.4?±?99.5 ml in women and 49.7?±?54.5 ml in men. Women manifested significantly higher BAT activity, by 9.4?±?8.1 % (p?=?0.03), than men. BAT volume correlated positively with total and spine BMD (r ²?=?0.40 and 0.49, respectively, p?<?0.02) in women and remained a significant predictor after adjustment for age, fat, and lean body mass (p?<?0.05). Total and spine BMD were higher in women who harbored visually detectable BAT on PET images than those without by 11?±?2 % (p?=?0.02) and 22?±?2 % (p?<?0.01), respectively. No associations were observed between BAT parameters and BMD in men.

Conclusions

This study demonstrated higher BMD among healthy women with more abundant BAT, independent of age and other body compositional parameters. This was not observed in men. The data suggest that brown adipogenesis may be physiologically related to modulation of bone density.     

Bone mass and vitamin D levels in women with a diagnosis of fibromyalgia

Summary

No differences in either bone mineral density or serum 25OHD levels have been found between 205 women with fibromyalgia (both pre- and postmenopausal) and their controls. However, a lack of the expected 25OHD summer rise was observed in patients.

Introduction

Contradictory data have been published regarding a possible association between fibromyalgia and osteoporosis or hypovitaminosis D. Most studies, however, have been performed in small size samples and have excluded postmenopausal women. We decided to study this association in a larger sample of fibromyalgia patients including both pre- and postmenopausal women.

Methods

Two hundred five patients were recruited from a clinic specializing in fibromyalgia and 205 healthy controls were enrolled from the census of a Primary Care Center. Controls were matched with patients by age and the time of the year they were included in the study. Bone mineral density (BMD) was measured by DXA. Serum 25OHD, iPTH, P1NP, and CTX were also determined.

Results

BMD was similar in both groups (lumbar spine, 0.971?±?0.146 g/cm² in patients and 0.970?±?0.132 g/cm² in controls; femoral neck, 0.780?±?0.122 g/cm² and 0.785?±?0.117 g/cm², respectively). 25OHD levels were also similar: 23.0?±?9.5 ng/ml and 24.1?±?9.6 ng/ml. However, while controls showed the usual summer rise in 25OHD, fibromyalgia patients did not. PTH did not show seasonal changes, but on average was higher in patients (51 pg/ml vs. 48 pg/ml; p?=?0.034). P1NP or CTX were similar in both groups.

Conclusions

No differences in BMD were found between patients and controls. As for 25OHD, a lack of its expected summer rise was observed. It is doubtful whether this has any homeostatic consequence. We consider that the association reported in other studies is merely circumstantial, and not due to the intrinsic characteristics of these disorders.     

Effect of denosumab on bone mineral density and biochemical markers of bone turnover: 8-year results of a phase 2 clinical trial

Summary

In a phase 2 study, continued denosumab treatment for up to 8 years was associated with continued gains in bone mineral density and persistent reductions in bone turnover markers. Denosumab treatment was well tolerated throughout the 8-year study.

Introduction

The purpose of this study is to present the effects of 8 years of continued denosumab treatment on bone mineral density (BMD) and bone turnover markers (BTM) from a phase 2 study.

Methods

In the 4-year parent study, postmenopausal women with low BMD were randomized to receive placebo, alendronate, or denosumab. After 2 years, subjects were reallocated to continue, discontinue, or discontinue and reinitiate denosumab; discontinue alendronate; or maintain placebo for two more years. The parent study was then extended for 4 years where all subjects received denosumab.

Results

Of the 262 subjects who completed the parent study, 200 enrolled in the extension, and of these, 138 completed the extension. For the subjects who received 8 years of continued denosumab treatment, BMD at the lumbar spine (N?=?88) and total hip (N?=?87) increased by 16.5 and 6.8 %, respectively, compared with their parent study baseline, and by 5.7 and 1.8 %, respectively, compared with their extension study baseline. For the 12 subjects in the original placebo group, 4 years of denosumab resulted in BMD gains comparable with those observed during the 4 years of denosumab in the parent study. Reductions in BTM were sustained over the course of continued denosumab treatment. Reductions also were observed when the placebo group transitioned to denosumab. Adverse event profile was consistent with previous reports and an aging cohort.

Conclusion

Continued denosumab treatment for 8 years was associated with progressive gains in BMD, persistent reductions in BTM, and was well tolerated.     

Denosumab significantly increases bone mineral density and reduces bone turnover compared with monthly oral ibandronate and risedronate in postmenopausal women who remained at higher risk for fracture despite previous suboptimal treatment with an oral bisphosphonate

Summary

Managing osteoporotic patients suboptimally adherent to bisphosphonates (BPs) is difficult. Such patients who remained at higher risk for fracture (≥1 risk factor) were transitioned to denosumab or a monthly oral BP. Denosumab-treated subjects had significantly greater increases in bone mineral density and decreases in bone turnover in this 12-month study.

Introduction

A clinical need exists to manage patients who are suboptimally adherent to oral BPs and remain at higher risk for fracture. Here, we compare the effects on bone mineral density (BMD) and bone turnover of transitioning such patients to denosumab or monthly oral BP (ibandronate or risedronate).

Methods

In two previous multicenter, open-label studies, postmenopausal women ≥55 years previously treated with, though suboptimally adherent to, a daily or weekly BP were randomized to denosumab 60 mg subcutaneously every 6 months (N?=?852) or oral BP 150 mg monthly (N?=?851) for 12 months. In this combined post-hoc analysis, a subset of higher risk subjects was identified, and the percentage changes from baseline in BMD and serum C-telopeptide of type I collagen (sCTX-1) were assessed.

Results

In the overall population, denosumab was associated with greater gains in BMD at 12 months than monthly oral BP at the total hip, femoral neck, and lumbar spine (p?<?0.0001 for all). In higher risk subjects, denosumab led to greater gains in BMD than oral BPs at the total hip (2.2 vs 0.8 %), femoral neck (1.8 vs 0.3 %), and lumbar spine (3.7 vs 1.4 %) (p?<?0.0001 for all). Denosumab also led to greater decreases in sCTX-1 in the overall population and higher risk subjects at months 1 and 6 (p?<?0.0001 for both). Adverse events and serious adverse events were generally similar between treatment groups.

Conclusions

Transitioning to denosumab was well tolerated and more effective in increasing BMD and reducing bone turnover than cycling to a monthly oral BP treatment in subjects who remained at higher fracture risk despite suboptimal BP treatment.