Association of serum sclerostin with bone mineral density, bone turnover, steroid and parathyroid hormones, and fracture risk in postmenopausal women: the OFELY study

Summary

Sclerostin is a key regulator of bone formation. In a population of 572 postmenopausal women (mean age, 67 years) followed prospectively for a median of 6 years, there was no significant association between baseline levels of serum sclerostin and incidence of all fractures which occurred in 64 subjects.

Introduction

Sclerostin, an osteocyte soluble factor, is a major negative regulator of osteoblastic activity. Circulating sclerostin levels were reported to increase with age and to be modestly associated with bone mineral density (BMD) and bone turnover, but there are no data on the association with fracture risk.

Methods

We investigated 572 postmenopausal women (mean age, 67?±?8.5 years) from the OFELY population-based cohort. The associations of serum sclerostin measured with a new two-site ELISA and spine and hip BMD by DXA, serum β-isomerized C-terminal crosslinking of type I collagen (CTX), intact N-terminal propeptide of type I collagen (PINP), intact PTH, 25-hydroxyvitamin D [25(OH)D], estradiol, testosterone, and fracture risk were analyzed. At the time of sclerostin measurements, 98 postmenopausal women had prevalent fractures. After a median of 6 years (interquartile range, 5–7 years) follow-up, 64 postmenopausal sustained an incident fracture.

Results

Serum sclerostin correlated positively with spine (r?=?0.35, p?<?0.0001) and total hip (r?=?0.25, <0.0001) BMD. Conversely, serum sclerostin was weakly negatively associated with the bone markers PINP (r?=??0.10, p?=?0.014) and CTX (r?=??0.13, p?=?0.0026) and with intact PTH (r?=??0.13, p?=?0.0064). There was no significant association of serum sclerostin with 25(OH)D, estradiol, free estradiol index, or testosterone. Serum sclerostin considered as a continuous variable or in quartiles was not significantly associated with the risk of prevalent or incident fracture.

Conclusion

Serum sclerostin is weakly correlated with BMD, bone turnover, and PTH in postmenopausal women. It was not significantly associated with the risk of all fractures, although the number of incident fractures recorded may not allow detecting a modest association.     

Sclerostin serum levels in prostate cancer patients and their relationship with sex steroids

Summary

The role of sclerostin on bone metabolism and its relation to sex steroids in patients with prostate cancer (PC) is not well known. We found that sclerostin levels are significantly increased in PC patients, particularly in those with androgen deprivation therapy (ADT), and there is an inverse relationship between sclerostin levels and testosterone.

Introduction

Recent studies have evaluated sclerostin levels in bone diseases as osteoporosis. However, there are few data in PC patients, particularly in patients with hypogonadism related to ADT. The aim of the present study was to compare serum sclerostin levels in ADT/non-ADT-treated PC patients and healthy controls and to evaluate their relationship with sex steroids and bone metabolism.

Methods

We performed a cross-sectional study involving 81 subjects: 25 ADT-treated PC patients, 34 PC patients without ADT treatment, and 22 healthy controls. We measured serum sclerostin levels, bone turnover markers, bone mineral density (BMD) in all individuals, and sex steroids levels in PC patients.

Results

Serum sclerostin levels were significantly higher in PC patients compared to those in control subjects. ADT-treated patients had significantly higher sclerostin levels than PC patients without ADT treatment: ADT 64.52?±?27.21 pmol/L, non-ADT 48.24?±?15.93 pmol/L, healthy controls 38.48?±?9.19 pmol/L, p?<?0.05. In PC patients, we found a negative relationship between serum sclerostin levels and androgens after age adjustment (total testosterone: r?=??0.309, p?=?0.029; bioavailable testosterone: r?=??0.280, p?=?0.049; free testosterone: r?=??0.299, p?=?0.035). We did not observe any relationship between sclerostin levels and bone turnover markers or BMD in any group.

Conclusions

Circulating sclerostin levels are significantly increased in patients with PC and particularly in those receiving ADT. The inverse relationship between serum sclerostin and testosterone in these patients suggests that androgens are key regulators of bone metabolism in this population.     

Comparison of two commercially available ELISAs for circulating sclerostin

Summary

This study investigates the performance and correlation of sclerostin measurements by two commercially available sclerostin ELISAs from TECOmedical and Biomedica. We found that the correlation between the results of two sclerostin assays is strong.

Introduction

Circulating sclerostin levels may provide insight into the pathophysiology of metabolic bone diseases such as osteoporosis. However, recent studies suggest that commercially available assays give different results. We compare the analytical performance of the two most used commercially available sclerostin ELISAs from TECOmedical and Biomedica.

Methods

Sclerostin levels were assessed in 20 paired serum, EDTA, and heparin plasma convenience samples from hospitalized patients. In addition, sclerostin was measured in serum samples from 34 patients with metabolic bone diseases and from 10 patients with chronic kidney disease (CKD). Samples from three healthy donors were used to determine stability and intra- and inter- assay precision.

Results

The average serum sclerostin concentration of all patients (n?=?64) was 0.713?±?0.58 ng/mL with the Biomedica assay and 0.734?±?0.43 ng/mL with the TECO assay (p?<?0.05). The results correlated strongly (r?=?0.9; p?<?0.0001), with Passing-Bablok regression showing a linear relationship but with a slight systematic and proportional difference between both assays. Sclerostin levels were about 30 % higher in plasma than in serum for both assays, while no significant difference was seen between EDTA and heparin plasma. Intra- and inter- precision were <10 % for TECO and <20 % for Biomedica. Samples were stable for up to three freeze-thaw cycles with both assays.

Conclusions

The two commercially available ELISAs for measuring circulating levels of sclerostin are comparable. However, given the small but statistically significant systematic and proportional differences between both assays, results and reference ranges will be assay-specific. Results will also be specific to serum or plasma.     

The relationship between BPAQ-derived physical activity and bone density of middle-aged and older men

Summary

The bone-specific physical activity questionnaire (BPAQ) accounts for activities that affect bone but has not been used in studies with older adults. Relationships exist between the BPAQ-derived physical activity and bone density in healthy middle-aged and older men but not men with prostate cancer. Disease-related treatments detrimental to bone should be considered when administering the BPAQ.

Introduction

The bone-specific physical activity questionnaire (BPAQ) was developed to account for bone-specific loading. In this retrospective study, we examined the relationship between BPAQ-derived physical activity and bone mineral density (BMD) in middle-aged and older men with and without prostate cancer.

Methods

Two groups, 36 healthy men and 69 men with prostate cancer receiving androgen suppression therapy (AST), completed the BPAQ and had whole body, total hip, femoral (FN) and lumbar spine BMD assessed by dual-energy X-ray absorptiometry.

Results

Past (pBPAQ), current (cBPAQ) and total BPAQ (tBPAQ) scores for the healthy men were related to FN BMD (pBPAQ r?=?0.36, p?=?0.030; cBPAQ r _s?=?0.35, p?=?0.034; tBPAQ r?=?0.41, p?=?0.014), and pBPAQ and tBPAQ were related to total hip (r _s?=?0.35, p?=?0.035 and r _s?=?0.36, p?=?0.029, respectively) and whole body BMD (r _s?=?0.44, p?=?0.007 and r _s?=?0.45, p?=?0.006, respectively). In men with prostate cancer, the BPAQ was not significantly associated with BMD. In stepwise regression analyses, body mass and tBPAQ predicted 30 % of the variance in total hip BMD (p?=?0.003), cBPAQ predicted 14 % of the variance in FN BMD (p?=?0.002), and body mass, age and tBPAQ predicted 47 % of the variance in whole body BMD (p?Conclusions Although BPAQ-derived estimates of physical activity are related to bone status in healthy middle-aged and older men, the adverse effect of AST on bone appears to obscure this relationship in men with prostate cancer.     

Sclerostin: a candidate biomarker of SCI-induced osteoporosis

Summary

We assessed several circulating proteins as candidate biomarkers of bone status in men with chronic spinal cord injury. We report that sclerostin is significantly associated with bone mineral content and bone density at all skeletal sites tested. We found no association between bone and any other tested biomarker.

Introduction

Spinal cord injury results in severe osteoporosis. To date, no circulating biomarker of spinal cord injury (SCI)-induced osteoporosis has been identified. We recently reported that circulating sclerostin is associated with bone density in chronic SCI. In this study, we assessed several circulating proteins as candidate biomarkers of bone in men with chronic SCI.

Methods

We assessed the relationship between bone mineral content or bone density and the following circulating bone-related proteins: sclerostin, DKK-1, soluble receptor activator of nuclear factor kappa B ligand, osteoprotegerin, osteocalcin, and c-telopeptide in 39 men with chronic SCI and 10 men with no SCI.

Results

After adjusting for age, lower sclerostin levels were significantly associated with lower bone mineral content and bone density at all skeletal sites tested (p?=?0.0002?0.03). No other circulating protein was associated with bone mineral content or bone mineral density (p?=?0.18?0.99).

Conclusion

These findings suggest that circulating sclerostin reflects the severity of bone loss and is a candidate biomarker of osteoporosis severity in chronic SCI.     

Skeletal health in adult patients with classic galactosemia

Summary

This study evaluated bone health in adults with galactosemia. Associations between bone mineral density (BMD) and nutritional and biochemical variables were explored. Calcium level predicted hip and spine BMD, and gonadotropin levels were inversely associated with spinal BMD in women. These results afford insights into management strategies for these patients.

Introduction

Bone loss is a complication of galactosemia. Dietary restriction, primary ovarian insufficiency in women, and disease-related alterations of bone metabolism may contribute. This study examined relationships between clinical factors and BMD in patients with galactosemia.

Methods

This cross-sectional sample included 33 adults (16 women) with classic galactosemia, mean age 32.0?±?11.8 years. BMD was measured by dual-energy X-ray absorptiometry, and was correlated with age, height, weight, fractures, nutritional factors, hormonal status, and bone biomarkers.

Results

There was a significant difference in hip BMD between women and men (0.799 vs. 0.896 g/cm², p?=?0.014). The percentage of subjects with BMD-Z <?2.0 was also greater for women than men [33 vs. 18 % (spine), 27 vs. 6 % (hip)], and more women reported sustaining fractures. Bivariate analyses yielded correlations between BMI and BMD-Z [at the hip in women (r?=?0.58, p?<?0.05) and spine in men (r?=?0.53, p?<?0.05)]. In women, weight was also correlated with BMD-Z (r?=?0.57, p?<?0.05 at hip), and C-telopeptides (r?=??0.59 at spine and ?0.63 hip, p?<?0.05) and osteocalcin (r?=??0.71 at spine and ?0.72 hip, p?<?0.05) were inversely correlated with BMD-Z. In final regression models, higher gonadotropin levels were associated with lower spinal BMD in women (p?=?0.017); serum calcium was a significant predictor of hip (p?=?0.014) and spine (p?=?0.013) BMD in both sexes.

Conclusions

Bone density in adults with galactosemia is low, indicating the potential for increased fracture risk, the etiology of which appears to be multifactorial.     

Relative influence of heritability,environment and genetics on serum sclerostin

Summary

We determined factors associated with serum sclerostin in 446 Afro-Caribbean family members. Age, weight, sex, diabetes and kidney function were associated with sclerostin. Sclerostin was heritable, and nine SNPs in the SOST gene region were associated with sclerostin. Variation in serum sclerostin is a heritable factor that is determined by both genetic and environmental factors.

Introduction

Sclerostin, encoded by the SOST gene, is a Wnt inhibitor that regulates bone mineralization and is a candidate gene locus for osteoporosis. However, little is known about the genetic and non-genetic sources of inter-individual variation in serum sclerostin levels.

Methods

Serum sclerostin was measured in 446 Afro-Caribbean men and women aged 18+ from seven large, multigenerational families (mean family size, 64; 3,840 relative pairs). Thirty-six common single nucleotide polymorphisms (SNP) were genotyped within a 100 kb region encompassing the gene encoding sclerostin (SOST). Genetic and non-genetic factors were tested for association with serum sclerostin.

Results

Mean serum sclerostin was 41.3 pmol/l and was greater in men than in women (P?<?0.05). Factors associated with higher serum sclerostin were increased age and body weight, male sex, diabetes and decreased glomerular filtration rate, which collectively accounted for 25.4 % of its variation. Residual genetic heritability of serum sclerostin was 0.393 (P?<?0.0001). Nine SNPs reached nominal significance with sclerostin. Three of those nine SNPs represented independent association signals (rs851056, rs41455049 and rs9909172), which accounted for 7.8 % of the phenotypic variation in sclerostin, although none of these SNPs surpassed a Bonferroni correction for multiple comparisons.

Conclusions

Serum sclerostin is a heritable trait that is also determined by environmental factors including age, sex, adiposity, diabetes and kidney function. Three independent common SNPs within the SOST region may collectively account for a significant proportion of the variation in serum sclerostin.     

Serum extracellular secreted antagonists of the canonical Wnt/β-catenin signaling pathway in patients with Cushing’s syndrome

Summary

Patients with endogenous hypercortisolism have higher sclerostin, but do not differ in Dickkopf 1 (Dkk1) or secreted frizzled-related protein 1 (SFRP1) levels as compared to healthy control.

Introduction

Endogenous Cushing’s syndrome (CS), usually affecting young and otherwise healthy patients, is a good model to validate the effects of supraphysiological levels of glucocorticoids in humans. This study evaluates circulating levels of extracellular antagonists of the Wnt/β-catenin signaling pathway (sclerostin, Dkk1, SFRP1) in patients with CS versus healthy individuals.

Methods

Forty patients with clinically and biochemically evident CS and 40 sex-, age-, and body mass index-matched healthy subjects provided fasting serum samples for sclerostin, SFRP1 and Dkk1, along with bone turnover markers.

Results

Patients with CS had higher sclerostin levels (34.5 (30.3–37.1) pmol/L) versus healthy individuals (29.9 (24.3–36.8) pmol/L) (p?=?0.032). Differences in sclerostin were due to the lack of lower sclerostin values rather than an increase in protein levels above the upper limits of the healthy control. The odds of sclerostin levels being higher than 30 pmol/L were greater in patients with CS as compared with the odds in healthy subjects (odds ratio?=?3.81 95 % confidence interval 1.45–10.02) (p?=?0.01). It coexisted with suppressed bone formation and unchanged bone resorption markers. Dkk1, SFRP1 did not differ from the control group.

Conclusions

Of all the tested proteins (sclerostin, Dkk1, SFRP1), only sclerostin showed a significant difference when contrasting CS with healthy subjects. Hypercortisolism might prevent the down-regulation of sclerostin. Targeting sclerostin seems to be a promising therapeutic approach to treating osteoporosis in patients with CS.     

The rhPTH treatment elevates plasma secreted protein acidic and rich in cysteine levels in patients with osteoporosis

Summary

The secreted protein acidic and rich in cysteine (SPARC), also known as osteonectin, plays an important role in osteoblast formation, maturation, and survival. Here, we report the effects of recombinant human parathyroid hormone (1-34) [rhPTH (1-34)], a bone formation-stimulating agent, and elcatonin on plasma SPARC levels in patients with osteoporosis. The rhPTH (1-34) treatment significantly increased plasma SPARC levels, and the change of plasma SPARC correlated positively with changes of lumbar bone mineral density (BMD) at L2–L4. These results unveil that SPARC may be a novel marker related to the regulation of bone formation.

Introduction

rhPTH (1-34) is known to influence osteoclast maturation and activity through modulation of osteoblast-derived cytokines. SPARC is the most abundant noncollagenous extracellular matrix protein in the bone. So far, however, no study has reported the effects of rhPTH (1-34) administration on plasma SPARC levels in patients with osteoporosis. The purpose of this study was to compare the response of SPARC and BMD to rhPTH (1-34) and elcatonin in postmenopausal women with osteoporosis.

Methods

Women were randomized to either once-daily subcutaneous injection of rhPTH (1-34) (20 μg, N?=?89) or once-weekly intramuscular injection of elcatonin (200 U, N?=?35) for 12 months. Plasma biochemical markers of bone turnover and BMD were measured at baseline, 6 and 12 months after treatment.

Results

At baseline, plasma SPARC levels correlated positively with lumbar spine BMD in all patients (r?=?0.45, p?=?0.001). Compared with baseline, at 12 months, rhPTH (1-34) significantly increased lumbar spine BMD and plasma SPARC levels (p?=?0.008 and p?=?0.001, respectively), whereas elcatonin was ineffective. More importantly, the changes of plasma SPARC correlated positively with changes of lumbar BMD at L2–L4 (r?=?0.47, p?=?0.001) in the rhPTH (1-34)-treated group, but not in the elcatonin group.

Conclusion

The increase in plasma SPARC levels during the rhPTH (1-34) treatment may have contributed to the anabolic effect on bone formation, and SPARC may be a novel marker related to the regulation of bone formation.     

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.     

An investigation of the association between omega 3 FA and bone mineral density among older adults: results from the National Health and Nutrition Examination Survey years 2005–2008

Summary

The relation of omega 3 fatty acids (n-3 FA) with bone mineral density (BMD) was assessed among adults >60 years; NHANES data (2005–2008). The association of dietary n-3 FA with measures of hip BMD was equivocal, but n-3 FA supplement use was significantly associated with higher spine BMD—a finding that deserves further study.

Introduction

Associations between polyunsaturated fatty acids and bone mineral density are not well understood.

Purpose

To evaluate the cross-sectional relation between dietary omega 3 fatty acid intake (specifically docosahexaenoic acid, eicosapentaenoic acid, and octadecatetraenoic) and BMD at the hip and spine among older adults.

Methods

Omega 3 FA intake (g/day) was assessed from two 24-h recalls using the National Health and Nutrition Examination Survey (NHANES, in 2005–2008); and omega 3 FA supplement use (yes/no) via questionnaire. Multivariable regression models were developed to explain variance in femoral neck, total femur, and lumbar spine BMD among 2,125 men and women over 60 years.

Results

Mean age was 70 years. In adjusted models, dietary omega 3 FA were marginally associated with greater femoral neck BMD (p?=?0.0505), but not with total femur BMD (p?=?0.95) or lumbar spine BMD (p?=?0.74). Omega 3 supplement use was significantly positively associated with lumbar spine BMD (p?=?0.005) but not with femoral neck or total femur BMD.

Conclusions

Dietary intakes of omega 3 FA were marginally associated with femoral neck BMD; however, omega 3 supplement use was significantly associated with higher lumbar spine BMD in older adults. These results emphasize the need for assessment of total omega 3 intakes (diet and supplements) to provide a greater range of intake and a more accurate picture of the relation between omega 3 FA and BMD.     

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.     

Fibroblast growth factor 21 (FGF21) and bone: is there a relationship in humans?

Summary

In animals, high fibroblast growth factor 21 (FGF21) states improve insulin resistance but induce bone loss. Whether FGF21 relates to bone mineral density (BMD) is unknown in humans. Contrary to prediction from animal findings, we found higher FGF21 levels associating with greater BMD in women, independent of age and body composition.

Introduction

Recent laboratory studies suggest that FGF21 is involved in reciprocal regulation of bone and energy homeostasis. Systemic administration of FGF21 protects animals from obesity and diabetes but causes severe bone loss, smothering the enthusiasm over FGF21 as a potential antiobesity therapeutic. To date, there is no information on whether FGF21 relates to BMD in humans. We thus studied the relationship between plasma FGF21 levels and BMD in healthy adults.

Methods

Fasting plasma FGF21 levels were measured by enzyme-linked immunosorbent assay and body composition by dual-energy X-ray absorptiometry.

Results

Among 40 healthy volunteers (age 32?±?10 year, 16 women), men had significantly higher lean body mass (p?<?0.01) and total BMD (p?<?0.05), and lower percent body fat than women (p?<?0.01). Median plasma FGF21 levels were not different between the sexes. While there was no association between FGF21 concentrations and body composition in men, FGF21 levels correlated positively with fat mass (p?<?0.01) in women. In men, no significant correlation between FGF21 with BMD was observed. However, in women, FGF21 correlated positively with total BMD (R ²?=?0.69, p?=?0.003) and spine BMD (R ²?=?0.76, p?=?0.001); the correlation remained significant after adjusting for age, ethnicity, and body composition.

Conclusions

This study reveals for the first time a strong positive association between plasma FGF21 levels and BMD in healthy women, suggesting the association between bone loss and high FGF21 states in animals may not be directly translated to humans in physiologic states. We hypothesize that FGF21 may increase bone mass particularly in women through paracrine mechanisms in the bone–adipose interface.     

Use of risedronate to prevent bone loss following a single course of glucocorticoids: findings from a proof-of-concept study in inflammatory bowel disease

Summary

We performed a randomised controlled trial (RCT) to determine whether risedronate 35 mg once weekly prevents bone loss following an 8-week reducing course of prednisolone given for an exacerbation of inflammatory bowel disease (IBD). The greatest change in bone mineral density (BMD) was at Ward’s triangle (WT), which fell by 2.2% in the placebo group, compared with a reduction of 0.8% in the risedronate group.

Introduction

Whether bisphosphonates can prevent bone loss associated with intermittent glucocorticoid (GC) therapy is unknown, reflecting the difficulty in performing RCTs in this context.

Method

To explore the feasibility of RCTs to examine this question, lumbar spine (LS; L2–4) and hip dual X-ray absorptiometry (DXA) scans were performed in 78 patients commencing a GC therapy course for a relapse of IBD. They were then randomised to receive placebo or risedronate 35 mg weekly for 8 weeks, after which the DXA scan was repeated.

Results

For LS BMD, there was no change in the placebo group (0.1?±?0.4, p?=?0.9), but there was an increase after risedronate (0.8?±?0.4, p?=?0.04; mean%?±?SEM by paired Student’s t test). There were small decreases in both groups at the total hip (?0.5?±?0.3, p?=?0.04; ?0.5?±?0.3, p?<?0.05, placebo and risedronate, respectively). At WT, BMD fell after placebo (?2.2?±?0.5, p?=?0.001) but not risedronate (?0.8?±?0.5, p?=?0.09; p?=?0.05 for between-group comparison).

Conclusion

RCTs can be used to examine whether bisphosphonates prevent bone loss associated with intermittent GC therapy, providing metabolically active sites such as WT are employed as the primary outcome.     

Social disadvantage, bone mineral density and vertebral wedge deformities in the Tasmanian Older Adult Cohort

Summary

The relationship between social disadvantage and bone mineral density (BMD) is complex and remains unclear; furthermore, little is known of the relationship with vertebral deformities. We observed social disadvantage to be associated with BMD for females, independent of body mass index (BMI). A lower prevalence of vertebral deformities was observed for disadvantaged males.

Introduction

The relationship between social disadvantage and BMD appears complex and remains unclear, and little is known about the association between social disadvantage and vertebral wedge deformities. We examined the relationship between social disadvantage, BMD and wedge deformities in older adults from the Tasmanian Older Adult Cohort.

Methods

BMD and wedge deformities were measured by dual-energy X-ray absorptiometry and associations with extreme social disadvantage was examined in 1,074 randomly recruited population-based adults (51 % female). Socioeconomic status was assessed by Socio-economic Indexes for Areas values derived from residential addresses using Australian Bureau of Statistics 2001 census data. Lifestyle variables were collected by self-report. Regression models were adjusted for age, BMI, dietary calcium, serum vitamin D (25(OH)D), smoking, alcohol, physical inactivity, calcium/vitamin D supplements, glucocorticoids and hormone therapy (females only).

Results

Compared with other males, socially disadvantaged males were older (65.9 years versus 61.9 years, p?=?0.008) and consumed lower dietary calcium and alcohol (both p?≤?0.03). Socially disadvantaged females had greater BMI (29.9?±?5.9 versus 27.6?±?5.3, p?=?0.002) and consumed less alcohol (p?=?0.003) compared with other females. Socially disadvantaged males had fewer wedge deformities compared with other males (33.3 % versus 45.4 %, p?=?0.05). After adjustment, social disadvantage was negatively associated with hip BMD for females (p?=?0.02), but not for males (p?=?0.70), and showed a trend for fewer wedge deformities for males (p?=?0.06) but no association for females (p?=?0.85).

Conclusions

Social disadvantage appears to be associated with BMD for females, independent of BMI and other osteoporosis risk factors. A lower prevalence of vertebral deformities was observed for males of extreme social disadvantage. Further research is required to elucidate potential mechanisms for these associations.     

Prevalence of femoro-acetabular impingement in international competitive track and field athletes

Purpose

The aim of our study was to analyse the prevalence of femoro-acetabular impingement (FAI) in national elite track and field athletes compared to peers using magnetic resonance imaging (MRI) and clinical examination including impingement tests.

Methods

A total of 44 participants (22 national elite track and field athletes and 22 non-athletes) underwent an MRI for radiological findings associated with FAI, including alpha angle, lateral centre edge angle (CEA), findings of labral and cartilage lesions. The study group was furthermore investigated by the hip outcome score (HOS) and a clinical hip examination including range of motion (ROM) and impingement tests.

Results

Concerning the cam impingement, there was a significant difference measured by mean alpha angle between the athlete group (52.2?±?7.29°) and the control group (48.1?±?5.45°, P?=?0.004). Eleven athletes showed a cam impingement, while two probands of the control group had a pincer impingement and one a mixed form (P?=?0.0217). There was no statistically significant difference concerning the CEA upon evaluating pincer impingement. Seven track and field athletes had a positive impingement test, whereof three had an increased alpha angle >55°. No participant of the control group showed pathological results in the impingement test (P?=?0.0121).

Conclusions

MRI evidence and clinical examination suggest that cam impingement is more common in elite athletes in comparison to non-athletes. At a professional level, the intense practice of track and field athletics is susceptible for FAI.     

Has sclerostin a true endocrine metabolic action complementary to osteocalcin in older men?

Summary

The reported association between sclerostin and diabetes mellitus or abdominal fat may be biased by body size and bone mass. In older men, the association between serum sclerostin levels and metabolic syndrome lost significance after adjustment for bone mass. The association between sclerostin and energy metabolism needs further clarification.

Introduction

Sclerostin is associated with abdominal fat, but this relationship may be biased since both are associated with body size and bone mass. Osteocalcin is a bone-derived hormone regulating energy metabolism. We assessed the association between serum sclerostin and metabolic syndrome (MetS) accounting for whole body mineral content (BMC) and osteocalcin.

Methods

We studied 694 men aged 51–85 who had serum osteocalcin and sclerostin measurements.

Results

Sclerostin was higher in 216 men with MetS compared with those without MetS (p?<?0.005). Average sclerostin level increased significantly across the increasing number of MetS components. In multivariable models, higher sclerostin was associated with higher odds of MetS (odds ratio (OR)?=?1.24/1 standard deviation (SD) increase [95 % confidence interval (95 % CI), 1.01–1.51]; p?<?0.05). After further adjustment for BMC, the association of MetS with sclerostin lost significance, whereas that with osteocalcin remained significant. Men who were simultaneously in the highest sclerostin quartile and the lowest osteocalcin quartile had higher odds of MetS (OR?=?2.14 [95 % CI, 1.15–4.18]; p?<?0.05) vs. men being in the three lower sclerostin quartiles and three upper osteocalcin quartiles. After adjustment for whole body BMC, the association lost significance.

Conclusions

Higher sclerostin level is associated with MetS severity; however, this association may be related to higher whole body BMC. The adjustment for BMC had no impact on the association between MetS and osteocalcin. Clinical cross-sectional studies do not elucidate the potential role of sclerostin in the regulation of energy metabolism and direct experimental approach is necessary.

     

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.     

Circulating activin-A is elevated in postmenopausal women with low bone mass: the three-month effect of zoledronic acid treatment

Summary

Activin-A is expressed in bone and seems to regulate osteoclastogenesis. In this study, serum activin-A was increased in postmenopausal women with low bone mass and was positively correlated to age and negatively to lumbar spinal bone mineral density (BMD). Serum activin-A levels did not change 3 months after zoledronic acid infusion.

Introduction

The aims of the study were to evaluate prospectively the circulating activin-A levels in postmenopausal women with low bone mass and explore possible correlations with clinical and laboratory data, as well as the 3-month effect of zoledronic acid infusion.

Methods

Postmenopausal women with low bone mass assigned to receive zoledronic acid infusion (Patients, n?=?47) and age-matched, postmenopausal women with normal bone mass (Controls, n?=?27) were recruited on an outpatient basis. Main outcome measurement was serum activin-A levels.

Results

Serum activin-A was higher in patients at baseline compared to controls (p?<?0.001) and activin-A in the serum of patients and controls was positively correlated with age (Spearman’s coefficient of correlation [rs]?=?0.325; p?=?0.005) and negatively with lumbar spinal (LS) BMD (rs?=??0.425; p?<?0.001). In multiple linear regression analysis, only age (B?=?8.93; 95 % CI?=?4.39–13.46; p?<?0.001) was associated with serum activin-A levels at baseline, independent from group (patients or controls), previous anti-osteoporotic treatment, LS BMD and follicle-stimulating hormone. Circulating activin-A levels were not affected 3 months after zoledronic acid infusion.

Conclusions

Serum activin-A is increased in postmenopausal women with low bone mass compared with postmenopausal women with normal bone mass and is positively correlated to age and negatively to LS BMD.