Does Quantitative Ultrasound of Bone Reflect More Bone Mineral Density Than Bone Microarchitecture?

Relationships among quantitative ultrasound of bone (QUS), bone mineral density (BMD) and bone microarchitecture have been poorly investigated in human calcaneus.Twenty-four specimens, from 12 men and 12 women (mean age 78 +/- 10 years; range 53-93), removed from cadavers were studied. The feet were axially sectioned above the ankle. Two variables were measured for QUS (Achilles, Lunar): broadband ultrasound attenuation (BUA) and speed of sound (SOS). A third variable, the stiffness index (SI), which is a combination of both BUA and SOS, was also calculated. BMD (a lateral view) was measured on a QDR 2000 densitometer (Hologic). Bone microarchitecture was assessed by computed tomography (CT) using a conventional CT-system. Fifteen sagittal sections (1 mm in width and 2 mm apart) were selected for CT. Methods used for characterizing bone microarchitecture consisted in structural (trabecular network characterization) and a fractal analyses. The relationships between QUS and bone microarchitecture were assessed by simple linear regression analysis with and without adjustment for BMD (partial correlation) and by backward stepwise regression analysis. Strong relationships were found between BMD and QUS. Adjusted r(2) values were 0.545 for SOS and 0.717 for SI. Two microarchitectural variables were also significantly correlated with both SOS and SI: apparent trabecular separation (App Tr Sp) and trabecular bone pattern factor (App TBPF). After adjustment for BMD few correlations between QUS and microarchitectural variables were always significant. Adjusted squared semipartial coefficients of correlation (rsp2) values between SOS and bone microarchitecture were 6%, 6.8%, 13.2% and 4.6% for App BV/TV, App Tr Sp, App TBPF and fractal dimension (FD), respectively. For SI, corresponding figures were 3.7%, 4.1%, 5.2% and 3.2%. Backward stepwise regression analysis using BMD and microarchitecture showed a slight increase of r(2) values that varied from 8.4% for SI to 17.8% for SOS, compared with BMD alone. The current study suggests that although BMD is a major determinant of acoustic properties of human calcaneus, significant density independent relationships with bone microarchitecture should also be taken into account.     

Does Quantitative Ultrasound of Bone Reflect More Bone Mineral Density Than Bone Microarchitecture?

Relationships among quantitative ultrasound of bone (QUS), bone mineral density (BMD) and bone microarchitecture have been poorly investigated in human calcaneus. .Twenty-four specimens, from 12 men and 12 women (mean age 78 ± 10 years; range 53–93), removed from cadavers were studied. The feet were axially sectioned above the ankle. Two variables were measured for QUS (Achilles®, Lunar): broadband ultrasound attenuation (BUA) and speed of sound (SOS). A third variable, the stiffness index (SI), which is a combination of both BUA and SOS, was also calculated. BMD (a lateral view) was measured on a QDR 2000 densitometer (Hologic). Bone microarchitecture was assessed by computed tomography (CT) using a conventional CT-system. Fifteen sagittal sections (1 mm in width and 2 mm apart) were selected for CT. Methods used for characterizing bone microarchitecture consisted in structural (trabecular network characterization) and a fractal analyses. The relationships between QUS and bone microarchitecture were assessed by simple linear regression analysis with and without adjustment for BMD (partial correlation) and by backward stepwise regression analysis. Strong relationships were found between BMD and QUS. Adjusted r² values were 0.545 for SOS and 0.717 for SI. Two microarchitectural variables were also significantly correlated with both SOS and SI: apparent trabecular separation (App Tr Sp) and trabecular bone pattern factor (App TBPF). After adjustment for BMD few correlations between QUS and microarchitectural variables were always significant. Adjusted squared semipartial coefficients of correlation (rs_p²) values between SOS and bone microarchitecture were 6%, 6.8%, 13.2% and 4.6% for App BV/TV, App Tr Sp, App TBPF and fractal dimension (FD), respectively. For SI, corresponding figures were 3.7%, 4.1%, 5.2% and 3.2%. Backward stepwise regression analysis using BMD and microarchitecture showed a slight increase of r² values that varied from 8.4% for SI to 17.8% for SOS, compared with BMD alone. The current study suggests that although BMD is a major determinant of acoustic properties of human calcaneus, significant density independent relationships with bone microarchitecture should also be taken into account.     

Does Using Autograft Bone Chips Achieve Consistent Bone Ingrowth in Primary TKA?

Background  

Cementless fixation remains controversial in TKA due to the challenge of achieving consistent skeletal attachment. Factors predicting durable fixation are not clearly understood, but we presumed bone ingrowth could be enhanced by the quantity of host bone and application of autograft bone chips.     

Diabetes Mellitus: Does it Affect Bone?

Both diabetes and fractures affect a large proportion of older adults. Recent cohort studies indicate that diabetes itself is associated with increased risk of fracture of the hip, proximal humerus, and foot. Observational studies and animal models suggest that decreased bone strength in diabetes may contribute to fracture risk but this remains a controversial issue. Type 1 diabetes is associated with modest reductions in bone mineral density (BMD) but type 2 diabetes is often characterized by elevated BMD. This paradox of higher BMD but increased fracture risk in type 2 diabetes may be explained by a combination of more frequent falls and poorer bone quality. Diabetes can impact bone through multiple pathways, some with contradictory effects, including obesity, changes in insulin levels, higher concentrations of advanced glycation end products in collagen, hypercalciuria associated with glycosuria, reduced renal function, lower insulin-like growth factor-I, microangiopathy, and inflammation. A better understanding of how diabetes metabolism and treatments affect bone would improve fracture prevention efforts in older diabetic adults.     

Does Exercise Influence Pediatric Bone? A Systematic Review

Background

Periods of growth are thought to be the best time to increase bone mineral content, bone area, and areal bone mineral density (aBMD) through increased loading owing to high rates of bone modeling and remodeling. However, questions remain regarding whether a benefit of exercise is seen at all bone sites, is dependent on pubertal status or sex of the child, or whether other factors such as diet modify the response to exercise.

Questions/purposes

We asked: (1) Does bone-loading exercise in childhood consistently increase bone mineral content, bone area, or aBMD? (2) Do effects of exercise differ depending on pubertal status or sex? (3) Does calcium intake modify the bone response to exercise?

Methods

A literature search identified 22 unique trials for inclusion in this meta-analysis of the effect of exercise on bone changes by bone site, pubertal status, and sex. Sample sizes ranged from 16 to 410 subjects 3 to 18 years old with length of intervention ranging from 3 to 36 months. Fifteen of 22 trials were randomized (child randomized in nine, classroom/school randomized in six) and seven were observational trials. Ten trials were Level 2 and 11 were Level 3 based on the Oxford Centre for Evidence-Based Medicine criteria. Random effects models tested the difference (intervention mean effect–control mean effect) in percent change in bone mineral content, bone area, and aBMD. Meta-regression was used to identify sources of heterogeneity and funnel plots were used to assess publication bias.

Results

Children assigned to exercise had greater mean percent changes in bone mineral content and aBMD than children assigned to the control groups. Mean differences (95% CI) in bone mineral content percent change between intervention and control groups at total body (0.8; 95% CI, 0.3–1.3; p = 0.003), femoral neck (1.5; 95% CI, 0.5–2.5; p = 0.003), and spine (1.7; 95% CI, 0.4–3.1; p = 0.01) were significant with no differences in bone area (all p > 0.05). There were greater percent changes in aBMD in intervention than control groups at the femoral neck (0.6; 95% CI, 0.2–1.1; p = 0.006) and spine (1.2; 95% CI, 0.6–1.8; p < 0.001). Benefit of exercise was limited to children who were prepubertal (bone mineral content: total body [0.9; 95% CI, 0.2–1.7; p = 0.01], femoral neck [1.8; 95% CI, 0.0–3.5; p = 0.047], spine [3.7; 95% CI, 0.8–6.6; p = 0.01], and aBMD: femoral neck [0.6; 95% CI, −0.1–1.2; p = 0.07], spine [1.5; 95% CI, 0.7–2.3; p < 0.001]), with no differences among children who were pubertal (all p > 0.05). Changes in aBMD did not differ by sex (all p > 0.05), although the number of studies providing male-specific results was small (six of 22 eligible studies included boys). There was significant heterogeneity in bone mineral content and bone area for which a source could not be identified. Heterogeneity in spine aBMD was reduced by including calcium intake and intervention length as covariates. Three trials designed to determine whether calcium intake modified the bone response to exercise all reported a greater effect of exercise on leg bone mineral content in children randomized to receive supplemental calcium than those receiving placebo.

Conclusions

Exercise interventions during childhood led to 0.6% to 1.7% greater annual increase in bone accrual, with effects predominantly among children who were prepubertal. If this effect were to persist into adulthood, it would have substantial implications for osteoporosis prevention. It is important to identify sources of heterogeneity among studies to determine factors that might influence the bone response to increased exercise during growth.

Level of Evidence

Level II, therapeutic study.     

Does Bone Wax Induce a Chronic Inflammatory Articular Reaction?

Background  

Bone wax is used to control femoral neck bleeding during open femoroacetabular impingement (FAI) surgery. Despite its widespread use, only a few case reports and small case series describe side effects after extraarticular use. It is unclear whether intraarticular use of bone wax leads to such complications. However, during revision FAI surgery, we have observed various degrees of articular inflammatory reactions.     

Does Muscular Power Predict Bone Mineral Density in Young Adults?

The aim of this study was to explore the relationships between maximum power and bone variables in a group of young adults. Two hundred and one young adults (53 men and 148 women) whose ages range from 18 to 35 years voluntarily participated in this study. Weight and height were measured, and body mass index was calculated. Body composition, bone mineral content (BMC) and bone mineral density (BMD) were determined for each individual by dual-energy X-ray absorptiometry. Vertical jump was evaluated using a validated field test (Sargent test). The highest vertical jump was selected. Maximum power (P max, in watts) of the lower limbs was calculated accordingly. In young men, maximum power was positively correlated to whole body (WB) BMC (r = 0.65; p < 0.001), WB BMD (r = 0.41; p < 0.01), L1–L4 BMC (r = 0.54; p < 0.001), total hip (TH) BMC (r = 0.50; p < 0.001), femoral neck (FN) BMC (r = 0.35; p < 0.01), FN cross-sectional area (CSA) (r = 0.33; p < 0.05) and FN cross-sectional moment of inertia (CSMI) (r = 0.50; p < 0.001). In young women, maximum power was positively correlated to WB BMC (r = 0.48; p < 0.001), WB BMD (r = 0.28; p < 0.001), L1–L4 BMC (r = 0.34; p < 0.001), TH BMC (r = 0.43; p < 0.001), TH BMD (r = 0.21; p < 0.01), FN BMC (r = 0.42; p < 0.001), FN BMD (r = 0.31; p < 0.001), FN CSA (r = 0.41; p < 0.001), FN CSMI (r = 0.40; p < 0.001) and FN Z (r = 0.41; p < 0.01). The current study suggests that maximum power is a positive determinant of WB BMC, WB BMD, FN CSA, and FN CSMI in young men. It also shows that maximum power is a positive determinant of WB BMC, WB BMD, TH BMD, FN BMD, FN CSA, FN CSMI, and FN Z in young women.     

Does Hormone Replacement Normalize Bone Geometry in Adolescents With Anorexia Nervosa?

Young women with anorexia nervosa (AN) have reduced secretion of dehydroepiandrosterone (DHEA) and estrogen contributing to skeletal deficits. In this randomized, placebo‐controlled trial, we investigated the effects of oral DHEA + combined oral contraceptive (COC) versus placebo on changes in bone geometry in young women with AN. Eighty women with AN, aged 13 to 27 years, received a random, double‐blinded assignment to micronized DHEA (50 mg/day) + COC (20 µg ethinyl estradiol/0.1 mg levonorgestrel) or placebo for 18 months. Measurements of areal bone mineral density (aBMD) at the total hip were obtained by dual‐energy X‐ray absorptiometry at 0, 6, 12, and 18 months. We used the Hip Structural Analysis (HSA) program to determine BMD, cross‐sectional area (CSA), and section modulus at the femoral neck and shaft. Each measurement was expressed as a percentage of the age‐, height‐, and lean mass‐specific mean from an independent sample of healthy adolescent females. Over the 18 months, DHEA + COC led to stabilization in femoral shaft BMD (0.0 ± 0.5% of normal mean for age, height, and lean mass/year) compared with decreases in the placebo group (?1.1 ± 0.5% per year, p = 0.03). Similarly, CSA, section modulus, and cortical thickness improved with treatment. In young women with AN, adrenal and gonadal hormone replacement improved bone health and increased cross‐sectional geometry. Our results indicate that this combination treatment has a beneficial impact on surrogate measures of bone strength, and not only bone density, in young women with AN. © 2014 American Society for Bone and Mineral Research.     

Does Anastrozole Affect Bone Resorption Similarly in Early and Late Postmenopausal Women?

The aim of this study was to determine whether the bone-resorption response to anastrozole differed according to initial patient age in postmenopausal women with breast cancer in a cross-sectional study. Second-morning void urines were collected for measurement of urinary cross-linked N-telopeptide of type I collagen (uNTx, corrected for creatinine and log-transformed) from postmenopausal women, 99 with breast cancer on anastrozole (ABC), 88 with newly diagnosed breast cancer (NDBC), and 137 community-dwelling healthy control (HC) women. Bone mineral density (BMD) was also measured at the lumbar spine (LS, L2–L4) and the femoral neck (FN) in the ABC group. uNTx (nanomole bone collagen equivalents/millimole creatinine) levels increased with age in HC subjects. In patients <70 years, anastrozole treatment led to a significant increase in uNTx compared with age-related HC subjects (1.74 vs. 1.55, P < 0.005). Patients >70 years showed no such increase compared to HC (1.72 vs. 1.69, nonsignificant); however, NDBC women >70 years had uNTx levels significantly lower than HC women (1.59 vs. 1.69, P < 0.05). There was no difference in uNTx levels above and below the age of 70 years in NDBC women (1.56 vs. 1.59, nonsignificant). ABC women were more likely to have a positive LS BMD z score than age-matched controls. Anastrozole treatment increases bone turnover more in younger postmenopausal women with breast cancer than in older women compared to healthy controls. Higher LS BMD in ABC patients may help protect against fracture.     

How Does Bone Quality Differ Between Healthy-weight and Overweight Adolescents and Young Adults?

Background

Overweight youth have greater bone mass than their healthy-weight peers but sustain more fractures. However, it is unclear whether and how excess body fat influences bone quality in youth.

Questions/purposes

We determined whether overweight status correlated with three-dimensional aspects of bone quality influencing bone strength in adolescent and young adult females and males.

Methods

We categorized males (n = 103; mean age, 17 years) and females (n = 85; mean age, 18 years) into healthy-weight and overweight groups. We measured lean mass (LM) and fat mass (FM) with dual-energy x-ray absorptiometry (DXA). We used high-resolution peripheral quantitative CT to assess the distal radius (7% site) and distal tibia (8% site). Bone quality measures included total bone mineral density (Tt.BMD), total area (Tt.Ar), trabecular bone volume fraction (BV/TV), trabecular number (Tb.N), separation (Tb.Sp), and thickness (Tb.Th). We used multiple regression to compare bone quality between healthy-weight and overweight adolescents adjusting for age, ethnicity, limb length, LM, and FM.

Results

Overweight males had higher (10%–21%) Tt.BMD, BV/TV, and Tb.N and lower Tb.Sp at the tibia and lower Tt.Ar at the radius than healthy-weight males. No differences were observed between overweight and healthy-weight females. LM attenuated the differences in bone quality between groups in males while FM negatively predicted Tt.BMD, BV/TV, Tb.N, and Tb.Th.

Conclusions

Our data suggest overweight males have enhanced bone quality compared with healthy-weight males; however, when group differences are interpreted in the context of the mechanostat theory, it appears bone quality of overweight adolescents adapts to LM and not to greater FM.     

Does Integrated Fixation Provide Benefit in the Reconstruction of Posttraumatic Tibial Bone Defects?

Background

Limb salvage in the presence of posttraumatic tibial bone loss can be accomplished using the traditional Ilizarov method of distraction osteogenesis with circular external fixation. Internal fixation placed at the beginning of the consolidation phase, so-called integrated fixation, may allow for earlier removal of the external fixator but introduces concerns about cross-contamination from the additional open procedure and maintenance of bone regenerate stability.

Questions/purposes

Among patients deemed eligible for integrated fixation, we sought to determine: (1) Does integrated fixation decrease the time in the external fixator? (2) Is there a difference in the rate of complications between the two groups? (3) Are there differences in functional and radiographic results between integrated fixation and the traditional Ilizarov approach of external fixation alone?

Methods

Between January 2006 and December 2012, we treated 58 patients (58 tibiae) with posttraumatic tibial bone loss using the Ilizarov method. Of those, 30 patients (52%) were treated with the “classic technique” (external fixator alone) and 28 (48%) were treated with the “integrated technique” (a combination of an external fixator and plating or insertion of an intramedullary nail). During that period, the general indications for use of the integrated technique were closed physes, no active infection, and a healed soft tissue envelope located at the intended internal fixation site; the remainder of the patients were treated with the classic technique. Followup on 30 (100%) and 28 (100%) patients in the classic and integrated techniques, respectively, was achieved at a minimum of 1 year (mean, 3 years; range, 1–8 years). Adverse events were reported as problems, obstacles, and complications according to the publication by Paley. Problems and obstacles are managed by nonoperative and operative means, respectively; in addition, they resolve completely with treatment. Complications, according to the Paley classification, result in permanent sequelae. Functional and radiographic results were reported using the Association for the Study and Application of Methods of Ilizarov scoring system.

Results

Overall, there was a mean of four (range, 2–5) surgical procedures to complete the tibial reconstruction with a similar incidence of unplanned surgical procedures (obstacles) between the two groups (p = 0.87). Patients treated with integrated fixation spent less time in the external fixator, 7 months (range, 5–20 months) versus 11 months (range, 1–15 months; p < 0.001). There were seven problems, 15 obstacles, and zero complications in the classic group. Ten problems, 15 obstacles, and one complication occurred in the integrated fixation group. There was no difference in the severity (p = 0.87) or number (p = 0.40) of complications between both groups. Good to excellent Association for the Study and Application of Methods of Ilizarov function and bone scores were obtained in 100% and 98% of patients, respectively.

Conclusions

The integrated fixation method allows for a more efficient limb salvage surgical reconstruction in patients carefully selected for that approach, whereas the frequency of adverse events and ability to restore limb lengths was not different between the groups with the numbers available. Careful placement of external fixation pins is critical to decrease cross-contamination with planned internal fixation constructs. In this study of posttraumatic tibial bone defect reconstruction, good/excellent results were found in all patients after a mean of four surgical procedures; however, a larger multicenter prospective study would allow for more robust and generalizable conclusions.

Level of Evidence

Level III, therapeutic study.     

How Does Body Fat Influence Bone Mass in Childhood? A Mendelian Randomization Approach

Fat mass may be a causal determinant of bone mass, but the evidence is conflicting, possibly reflecting the influence of confounding factors. The recent identification of common genetic variants related to obesity in children provides an opportunity to implement a Mendelian randomization study of obesity and bone outcomes, which is less subject to confounding and several biases than conventional approaches. Genotyping was retrieved for variants of two loci reliably associated with adiposity (the fat mass and obesity‐related gene FTO and that upstream of the MC4R locus) within 7470 children from the Avon Longitudinal Study of Parents and Children (ALSPAC) who had undergone total body DXA scans at a mean of 9.9 yr. Relationships between both fat mass/genotypes and bone measures were assessed in efforts to determine evidence of causality between adiposity and bone mass. In conventional tests of association, both with and without height adjustment, total fat mass was strongly related to total body, spinal, and upper and lower limb BMC (ratio of geometric means [RGM]: 1.118 [95% CI: 1.112, 1.123], 1.110 [95% CI: 1.102, 1.119], 1.101 [95% CI: 1.093, 1.108], 1.146 [95% CI: 1.143, 1.155]; p < 10^?10 [adjusted for sex, height, and sitting height]). Equivalent or larger effects were obtained from instrumental variable (IV) regression including the same covariates (1.139 [95% CI: 1.064, 1.220], 1.090 [95% CI: 1.010, 1.177], 1.142 [95% CI: 1.049, 1.243], 1.176 [95% CI: 1.099, 1.257]; p = 0.0002, 0.03, 0.002, and 2.3^?6 respectively). Similar results were obtained after adjusting for puberty, when truncal fat mass was used in place of total fat, and when bone area was used instead of bone mass. In analyses where total body BMC adjusted for bone area (BA) was the outcome (reflecting volumetric BMD), linear regression with fat mass showed evidence for association (1.004 [95% CI: 1.002, 1.007], p = 0.0001). IV regression also showed a positive effect (1.031 [95% CI: 1.000, 1.062], p = 0.05). When MC4R and FTO markers were used as instruments for fat mass, similar associations with BMC were seen to those with fat mass as measured by DXA. This suggests that fat mass is on the causal pathway for bone mass in children. In addition, both directly assessed and IV‐assessed relationships between fat mass and volumetric density showed evidence for positive effects, supporting a hypothesis that fat effects on bone mass are not entirely accounted for by association with overall bone size.     

Does the Severity of Obesity Influence Bone Mineral Density Values in Premenopausal Women?

The aim of this study was to compare bone mineral content (BMC), bone mineral density (BMD), and geometric indices of hip bone strength among 3 groups of adult obese premenopausal women (severely obese, morbidly obese, and super morbidly obese). This study included 65 young adult premenopausal women whose body mass index (BMI) > 35 kg/m². They were divided into 3 groups using international cut-offs for BMI. Body composition and bone variables were measured by DXA. DXA measurements were completed for the whole body (WB), lumbar spine, total hip (TH), and femoral neck (FN). Geometric indices of FN strength (cross-sectional area, cross-sectional moment of inertia [CSMI], section modulus [Z], strength index [SI], and buckling ratio) were calculated by DXA. Results showed that age and height were not significantly different among the 3 groups. WB BMC values were higher in super morbidly obese women compared to severely and morbidly obese women. WB BMD, L1-L4 BMD, total hip BMD, FN BMD, cross-sectional area, CSMI, Z, and buckling ratio values were not significantly different among the 3 groups. SI values were lower in super morbidly obese compared to morbidly and severely obese women. In the whole population (n = 65), body weight, BMI, lean mass, fat mass, and trunk fat mass were positively correlated to WB BMC and negatively correlated to SI. Weight and lean mass were positively correlated to WB BMD and CSMI. Our findings suggest that the severity of obesity does not influence BMD values in premenopausal women.     

Bone Quality in Paget’s Disease of Bone

Paget’s disease of bone is produced by a localized increase in osteoclastic and osteoblastic activity which can progress slowly to involve an entire bone if untreated. A common feature is enlarged bones which are deformed, particularly in weight-bearing regions of the skeleton such as the lower extremity. Pathologic fractures may be a consequence, and nonunion of femoral fractures is not uncommon. Analyses of bone biopsies from patients with Paget’s disease indicate that there is a lower, heterogeneous degree of bone mineralization and a younger tissue age than that found in control bone. Pagetic bone also has less resistance to plastic deformation and a straighter crack path than control bone.     

How Long Does Antimycobacterial Antibiotic-loaded Bone Cement Have In Vitro Activity for Musculoskeletal Tuberculosis?

Background

Antibiotic-loaded bone cement is accepted as an effective treatment modality for musculoskeletal tuberculosis. However, comparative information regarding combinations and concentrations of second-line antimycobacterial drugs, such as streptomycin and amoxicillin and clavulanic acid, are lacking.

Questions/Purposes

(1) In antibiotic-loaded cement, is there effective elution of streptomycin and Augmentin^® (amoxicillin and clavulanic acid) individually and in combination? (2) What is the antibacterial activity duration for streptomycin- and amoxicillin and clavulanic acid -loaded cement?

Methods

Six different types of bone cement discs were created by mixing 40 g bone cement with 1 or 2 g streptomycin only, 0.6 g or 1.2 g Augmentin^® (amoxicillin and clavulanic acid) only, and a combination of 1 g streptomycin plus 0.6 g amoxicillin and clavulanic acid and 2 g streptomycin plus 1.2 g amoxicillin and clavulanic acid. Five bone discs of each type were incubated in phosphate buffered saline for 30 days with renewal of the phosphate buffered saline every day. The quantity of streptomycin and/or amoxicillin and clavulanic acid in eluates were measured by a liquid chromatography–mass spectrometry system, and the antimycobacterial activity of eluates against Mycobacterium tuberculosis H37Rv, were calculated by comparing the minimal inhibitory concentration of each eluate with that of tested drugs using broth dilution assay on microplate.

Results

Streptomycin was detected in eluates for 30 days (in 1 g and 2 g discs), whereas 1.2 g amoxicillin and clavulanate eluted until Day 7 and 0.6 g amoxicillin and clavulanate until Day 3. All eluates in streptomycin-containing discs (streptomycin only, and in combination with amoxicillin and clavulanic acid) had effective antimycobacterial activity for 30 days, while amoxicillin and clavulanate-only preparations were only active until Day 14. The antimycobacterial activity of eluates of 2 g streptomycin plus 1.2 g amoxicillin and clavulanate were higher than those of discs containing 1 g streptomycin plus 0.6 g amoxicillin and clavulanate until Day 3, without differences (Day 3, 1 g streptomycin plus 0.6 g amoxicillin and clavulanate: 17.5 ± 6.85 ug/mL; 2 g streptomycin plus 1.2 g amoxicillin and clavulanate: 32.5 ± 16.77 ug/mL; p = 0.109). After Day 7, however, values of the two combinations remained no different than that of Day 30 (Day 30, 1 g streptomycin plus 0.6 g amoxicillin and clavulanate: 0.88 ± 0.34 ug/mL; 2 g streptomycin plus 1.2 g amoxicillin and clavulanate: 0.59 ± 0.94 ug/mL; p = 0.107).

Conclusions

Streptomycin, in the form of antibiotic-loaded bone cement, had effective elution characteristics and antimycobacterial effects during a 30-day period, whereas amoxicillin and clavulanate only had effective elution and antimycobacterial characteristics during the early period of this study. The two drugs did not interfere with each other during the elution test.

Clinical Relevance

This research revealed that combinations of streptomycin and amoxicillin and clavulanate mixed with bone cement are effective for 30 days. Further trials to determine various different combinations of drugs are necessary to improve the effectiveness of treatments for musculoskeletal tuberculosis.

     

Does the Precision of Dual-Energy X-ray Absorptiometry for Bone Mineral Density Differ by Sex?

Given larger bone size in men, bone mineral density (BMD) precision might differ between sexes. This study compared dual-energy X-ray absorptiometry BMD precision of 3 International Society for Clinical Densitometry-certified technologists in older men and women. Each technologist scanned a cohort of 30 men and 30 women (total n = 180) by using a Lunar iDXA densitometer (GE Healthcare, Madison, WI). Each volunteer had 2 lumbar spine and bilateral hip scans with repositioning between examinations. BMD least significant change was calculated. Age and body mass index did not differ between men and women. Mean height and weight were greater in men, 174.6 cm ± 6.9 and 81.6 kg ± 11.1 respectively, (p < 0.0001) than in women, 161.5 cm ± 5.9/69.1 kg ± 14.2, respectively. Bone area was greater in men (p < 0.0001) at all sites. BMD least significant change was statistically better (p < 0.05) in women at the mean total femur (0.014 vs 0.018 g/cm²) and left femoral neck (0.025 vs 0.038 g/cm²), but not different at either total femur, the right femoral neck, or lumbar spine (all p > 0.05). In conclusion, statistically significant male/female differences in BMD precision were observed at the mean total femur and left femoral neck. Given the small magnitude of difference in g/cm² and inconsistent pattern, that is, no right femoral neck difference, there is virtually no clinical difference in BMD precision between sexes. These data do not support a need for sex-specific precision analyses.     

How Does?Bone Strength?Compare Across Sex,Site, and Ethnicity?

Background

The risk of fragility fractures in the United States is approximately 2.5 times greater among black and white women compared with their male counterparts. On average, men of both ethnicities have wider bones of greater cortical mass compared with the narrower bones of lower cortical mass among women. However, it remains uncertain whether the low cortical area observed in the long bones of women is consistent with their narrower bone diameter or if their cortical area is reduced beyond that which is expected for the sex differences in body size and external bone size.

Questions/purposes

We asked (1) do black and white women consistently have narrower bones of less strength across long bones compared with black and white men; and (2) do all long bones of black and white women have reduced cortical area compared with black and white men?

Methods

Peripheral quantitative CT was used to quantify bone strength and cross-sectional morphology from the major long bones of 125 white and 115 black adult men and women (20–35 years of age). Regression analyses were used to test for differences in bone strength and cortical area after for adjusting for either body size, bone size, or both.

Results

After adjusting bone strength for body size, regression analyses showed that black women had lower bone strength compared with black men (women: mean = 298.7–25,522 mg HA mm⁴, 95% confidence interval [CI], 270–27,692 mg HA mm⁴; men: mean = 381.6–30,945 mg HA mm⁴, 95% CI, 358.2–32,853 mg HA mm⁴; percent difference = 12%–38%, p = 0.06–0.0001). Similarly, white women also had lower bone strength compared with white men (women: mean = 229.5–22,892 mg HA mm⁴, 95% CI, 209.3–24,539 mg HA mm⁴; men: mean = 314.3–29,986 mg HA mm⁴, 95% CI, 297.3–31,331 mg HA mm⁴; percent difference = 27%–49%, p = 0.0001). All long bones of women for both ethnicities showed lower cortical area compared with men. After accounting for both body size and external bone size, black women (women: mean = 43.25–357.70 mm², 95% CI, 41.45–367.52 mm²; men: mean = 48.06–400.10 mm², 95% CI, 46.67–408.72; percent difference = 6%–25%, p = 0.02–0.0001) and white women (women: mean = 38.53–350.10 mm², 95% CI, 36.99–359.80 mm²; men: mean = 42.06–394.30 mm², 95% CI, 40.95–402.10 mm²; percent difference = 6%–22%, p = 0.02–0.0001) were shown to have lower cortical area than their male counterparts. Therefore, the long bones of women are not only more slender than those of men, but also show a reduced cortical area that is 6% to 25% greater than expected for their external size, depending on the bone being considered.

Conclusions

The long bones of females are not just a more slender version of male long bones. Women have less cortical area than expected for their body size and bone size, which in part explains their reduced bone strength when compared with the more robust bones of men.

Clinical Relevance

The outcome of this assessment may be clinically important for the development of diagnostics and treatment regimens used to combat fractures. Future work should look at how the relationship among parameters reported here translates to the more fracture-prone metaphyseal regions.