Reproductive, Menstrual and Menopausal Factors: Which Are Associated with Bone Mineral Density in Early Postmenopausal Women?

The associations between a number of reproductive and menopausal factors and bone mineral density (BMD) were studied in a sample of early postmenopausal women. The study included 580 women aged 45–61 years who completed a risk factor questionnaire containing sections on obstetric and menstrual history. BMD measurements were taken at the anteroposterior (AP) spine, greater trochanter, femoral neck, total radius and whole body, along with whole body bone mineral content (BMC). In analyses adjusting for key confounders, number of pregnancies was more strongly associated with increased BMD than number of live births at all sites (p<0.05 at femoral neck and total radius), and menstrual years was more strongly associated with increased BMD than years since menopause (p<0.05 at all sites). Hysterectomized women had a significantly higher adjusted mean BMD than non-hysterectomized women at all sites (AP spine: 0.999 g/cm² vs 0.941 g/cm², p<0.001), although there were no significant differences in BMD between hysterectomized women who had a bilateral oophorectomy and those whose ovaries were preserved. Negative associations between the duration of hot flushes and BMD were statistically significant (p<0.05) at the three non-hip sites. In multiple regression analyses containing all reproductive terms, duration of hormone replacement therapy (HRT) use, menstrual years and hysterectomy status were significantly associated with BMD at all five sites, whilst oral contraceptive use before the age of 23 years was significantly associated with increased BMD at all sites except the total radius. Breastfeeding duration, the duration of oral contraceptive use and premenopausal amenorrhea were found to have no association with BMD. Results for whole body BMC were consistent with those for the five BMD sites, across all the variables considered here. These findings confirm the importance of HRT use and duration of menses as predictors of BMD, whilst the results for hysterectomy status and early oral contraceptive use require further consideration. Received: 26 July 2000 / Accepted: 5 April 2001     

Does Route of Hysterectomy Affect Outcome in Obese and Nonobese Women?

Objective:

Our objective was to compare the surgical outcomes of obese women having hysterectomy according to the route (abdominal, vaginal, or laparoscopic) of the procedure.

Methods:

A chart review of 293 hysterectomy procedures was performed. Data were collected including operative and anesthesia time, estimated blood loss, change in hematocrit, hospital stay, complications, conversion to laparotomy, transfusion, and body mass index. An analysis of variance and a Newman-Keuls Multiple Comparison test were performed.

Results:

Obese women experienced a significant decrease in hospital days (2.5 versus 4.2) and reported blood loss (204 mL versus 455 mL) in the laparoscopic hysterectomy and vaginal hysterectomy groups compared with the abdominal hysterectomy group. No significant difference was found in obese women between laparoscopic and abdominal hysterectomy for time spent in surgery and under anesthesia. For obese and normal weight women, vaginal hysterectomy offered the shortest surgery, anesthesia times, and hospital stays.

Conclusions:

For normal and obese women, vaginal hysterectomy offered the shortest hospital stay and surgery time. In obese patients for whom vaginal hysterectomy is not possible, laparoscopic hysterectomy should be considered before abdominal hysterectomy, because the laparoscopic route reduced hospital time and blood loss.     

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.     

A Combination of Low Doses of 17β-Estradiol and Norethisterone Acetate Prevents Bone Loss and Normalizes Bone Turnover in Postmenopausal Women

The effects of 17β-estradiol (E₂) 1 mg combined with low doses of norethisterone acetate (NETA) on postmenopausal bone loss and turnover were investigated in a 2-year, randomized, double-masked, placebo-controlled trial. A total of 135 postmenopausal women with a lumbar spine bone mineral density (BMD) T-score between −2 and +2 were randomized to daily treatment with an oral tablet of either placebo, E₂ 1 mg/NETA 0.25 mg, or E₂ 1 mg/NETA 0.5 mg. Significant (p<0.001) increases in BMD at the lumbar spine (L1–4) were observed with E₂ 1 mg/NETA 0.25 mg (5.2%) and E₂ 1 mg/NETA 0.5 mg (5.4%) compared with placebo (−0.9%). The total hip BMD increased significantly in the E₂ 1 mg/NETA 0.25 mg (3.1%) and E₂ 1 mg/NETA 0.5 mg groups (3.3%) compared with placebo. At the femoral trochanter, the increase in BMD in the E₂ 1 mg/NETA 0.5 mg group (6.3%) was significantly different from the placebo group (0.8%), while that in the E₂ 1 mg/NETA 0.25 mg group (3.3%) was not. No statistical differences were found between the active groups and placebo for the change in BMD at the femoral neck. Significant increases in BMD at the distal radius and total body were found for both E₂ 1 mg/NETA 0.25 mg (0.9% and 2.5%, respectively) and E₂ 1 mg/NETA 0.5 mg (2.1% and 3.0%, respectively) compared with placebo (−0.7% and 0.4%, respectively).  At the end of the treatment, urinary pyridinoline type I collagen C-telopeptide had decreased by 65% and 60% in the E₂ 1 mg/NETA 0.25 mg and E₂ 1 mg/NETA 0.5 mg groups, respectively, while the mean serum concentrations of osteocalcin had decreased by 39% and 34%, bone-specific alkaline phosphatase by 32% and 29%, and C-terminal propeptide of type I collagen by 21% and 19% had decreased by 34-39%, 29-32%, and 19-21% in the E₂ 1 mg/NETA 0.25 mg and E₂ 1 mg/NETA 0.25 mg groups, respectively.  In conclusion, combinations of E₂ 1 mg and NETA 0.25 or 0.5 mg prevent bone loss in postmenopausal women at the lumbar spine, hip, distal radius and total body, and normalize bone turnover. Received: 12 March 1998 / Accepted: 31 August 1999     

Does Contrast Medium Administration in Organ Donors Affect Early Kidney Graft Function?

Since the upper age for organ donors has been raised, a higher incidence of preexistent organ damage and functional impairment is to be expected. Coronary artery sclerosis increases with age. It can only be diagnosed with certainty by coronary angiography. Since contrast medium administration may cause renal damage when risk factors are present, this study sought to establish whether angiography negatively influenced the early postoperative function of kidney grafts. We compared the clinical courses of 36 recipients of kidneys from donors in whom coronary angiography or levography had been performed with 36 recipients of kidneys from donors who had not been subjected to contrast medium. The results showed that the administration of contrast medium had no influence on renal function at 3 or 6 months after transplantation. In conclusion, fears that donor kidneys might be harmed by contrast medium appeared to therefore be unfounded.     

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.     

Matrix Delivery Transdermal 17β-Estradiol for the Prevention of Bone Loss in Postmenopausal Women

A total of 277 early postmenopausal women were enrolled in this placebo-controlled 2-year study to examine the efficacy of a matrix transdermal 17β-estradiol system, at three different dosages (25, 50 and 75 mg/day) combined with sequential oral dydrogesterone 20 mg/day, in preventing bone loss. At 2 years, the difference from placebo in percentage change from baseline of L1–4 lumbar spine bone mineral density (BMD) (assessed by dual-energy X-ray absorptiometry) was 4.7%± 0.7% with estradiol 25 mg/day, 7.3%± 0.7% with estradiol 50 mg/day and 8.7%± 0.7% with estradiol 75 mg/day (all values mean ± SEM). There were also significant increases in femoral neck, trochanter and total hip BMD with all doses of estradiol compared with placebo. Additionally, most patients had a significant gain (increase greater than 2.08%) in lumbar spine bone mass compared with placebo. Patients who received estradiol also experienced clinically significant and dose-related decreases in total serum osteocalcin, serum bone alkaline phosphatase and urinary C-telopeptide, with all three markers of bone turnover returning to premenopausal levels. Estradiol was well tolerated during the 2-year treatment period. Transdermal estradiol is effective and well tolerated at dosages between 25–75 mg/day in the prevention of bone loss in postmenopausal women; 25 mg/day offers an effective option for those women who cannot tolerate higher doses. Received: 30 June 1998 / Accepted: 22 September 1998     

Does Resection Line Involvement Affect Prognosis in Early Gastric Cancer Patients? An Italian Multicentric Study

Background Resection line involvement has been indicated as an important prognostic factor for gastric cancer. Its late detection renders the choice of treatment difficult for surgeons. Materials and Methods We describe the multicenter experience of a group of 11 patients with early gastric carcinoma (EGC) and positive resection confirmed at histological examination who did not undergo surgical retreatment for reasons of associated disease, surgical considerations on duodenal stump, or patient refusal. Results The gastric margin was involved in 4 patients, and 7 patients had duodenal resection line involvement. No surgical complications or postoperative deaths were observed. Five and 8-year survival was 100% and 86%, respectively. The only patient who relapsed did not have lymph node involvement and died from liver metastases, without local recurrence. Conclusions It is sometimes difficult to accurately define the resection line in gastric cancer surgery, especially in the early stages of disease, but because of the strongly negative prognostic value of an infiltrated margin, frozen sections are recommended if neoplastic invasion is suspected and a new resection is always recommended if possible. Nevertheless, the good prognosis of resected EGC patients with resection line involvement must be considered before submitting patients with associated diseases to radical surgical retreatment.     

Does Race Affect Outcomes in Total Joint Arthroplasty?

Background

Several studies suggest worse surgical outcomes among racial/ethnic minorities. There is a paucity of research on preoperative and postoperative pain, general health, and disease-specific measures in which race is the main subject of investigation; furthermore, the results are not conclusive.

Questions/purposes

(1) Do black patients have more severe or more frequent preoperative pain, well-being, general health, and disease-specific scores when compared with white patients? (2) Are there differences between black patients and white patients after hip or knee arthroplasty on those same measures?

Methods

In this retrospective study, we used an institutional arthroplasty registry to analyze data on 2010 primary arthroplasties (1446 knees and 564 hips) performed by one surgeon at a single institution. Cases from patients self-identifying as black (n = 105) and white (n = 1905) were compared (controlling for confounders, including age and ethnicity) on the following preoperative and postoperative patient-oriented outcomes: pain intensity/frequency as measured by a visual analog scale (VAS), Quality of Well-Being (QWB-7), SF-36, and WOMAC scores. T-tests, chi square, and multivariate analysis of covariance were used. Alpha was set at 0.05. Postoperative analysis was performed only on those cases that had a minimum followup of 1 year (mean, 3.5 years; range, 1–9 years). Of the 2010 arthroplasties, 37% (39 of 105) of those cases performed in black patients and 64% (1219 of 1905) of those performed in white patients were included in the final postoperative model (multivariate analysis of covariance).

Results

Black patients had more severe preoperative pain intensity (VAS: 8 ± 1.8 versus 8 ± 2.0, mean difference = 0.76 [95% confidence interval {CI}, 0.34–1.1], p < 0.001). Black patients also had worse well-being scores (QWB-7: 0.527 ± 0.04 versus 0.532 ± 0.05, mean difference = −0.01 [CI, −0.02 to 0.00], p = 0.037). Postoperatively, pain intensity (VAS: 1 ± 3.1 versus 1 ± 1.8, mean difference= 0.8 [CI, 0.19–1.4], p= 0.010) and (QWB-7: 0.579 ± 0.09 versus 0.607 ± 0.11, mean difference= −0.049 [CI, −0.08 to −0.01], p = 0.008) were different but without clinical significance.

Conclusions

Black patients underwent surgery earlier in life and with different preoperative diagnoses when compared with white patients. Black patients had worse preoperative baseline pain, well-being, general health, and disease-specific scores as well as worse postoperative scores. However, these differences were very narrow and without clinical significance. Notwithstanding, the relations of race with outcomes remain complex. Further investigations to recognize disparities and minimize or address them are warranted.

Level of Evidence

Level III, prognostic study.     

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.     

Polymorphisms in the CYP19 and AR Genes—Relation to Bone Mass and Longitudinal Bone Changes in Postmenopausal Women With or Without Hormone Replacement Therapy: The Danish Osteoporosis Prevention Study

Polymorphisms in the androgen receptor (AR) gene and genes encoding enzymes involved in synthesis of sex steroids (e.g., the CYP19 gene encoding aromatase) have recently received attention in osteoporosis research. In the Danish Osteoporosis Prevention Study, recent postmenopausal women were allocated to either hormone replacement therapy (HRT) or no treatment. We genotyped 1792 women for the CYP19 (TTTA)_n repeat [short (TTTA)_{n 7} or long (TTTA)_{n > 7}] the CYP19 C¹⁵⁵⁸-T, and the AR (CAG)_n repeat polymorphism [short (CAG)_{n < 22}, long (CAG)_{n 22}], and investigated associations with bone mineral density (BMD) and 5-year change in BMD. The CYP19 polymorphisms were in strong linkage disequilibrium. Perimenopausal bone mass or bone loss in untreated women was not associated with the CYP19 polymorphisms. In hormone-treated women, BMD increase in the femoral neck was highest (+0.3%/year) for long CYP19 alleles, lowest (–0.09%/year) for short alleles, and intermediate (–0.002%/year) in heterozygous women, P = 0.015. Differences were also significant in the lumbar spine, total hip, and ultradistal forearm. The C¹⁵⁵⁸-T T-allele was associated with a more pronounced response to HRT (P = 0.04, total hip). AR genotype was not related to BMD, but a modifying effect of sex hormone-binding globulin (SHBG) was present. In the highest SHBG quartile (SHBG > 95 nmol/1, n = 222), AR genotype was associated with baseline BMD (femoral neck: P < 0.001, total hip: P = 0.008), but without a clear gene dosage effect. We have demonstrated that polymorphisms in the CYP19 gene are associated with the magnitude of bone gain in response to HRT and that the (CAG)_n repeat polymorphism in the AR gene is associated with bone mass in women with high levels of SHBG. These findings emphasize the complexity of the genetics of bone mass and bone loss. Data was presented in part at the 30th European Symposium on Calcified Tissues, Rome, Italy, May 2003.     

Circulating Sex Steroids,Sex Hormone-Binding Globulin,and Longitudinal Changes in Forearm Bone Mineral Density in Postmenopausal Women and Men: The Tromsø Study

Bone loss during advancing age in women and men is partly the result of sex steroid deficiency. As the contribution of circulating sex steroids and sex hormone-binding globulin (SHBG) to bone loss remains uncertain, we sought to determine whether levels of sex steroids or SHBG predict change in bone mineral density (BMD) in women and men. A population-based study in the city of Tromsø of 6.5 years’ duration (range 5.4-7.4) included 927 postmenopausal women aged 37–80 years and 894 men aged 25–80 years. Total estradiol and testosterone, calculated free levels, and SHBG were measured at baseline, and BMD change at the distal forearm was determined using BMD measurements in 1994–1995 and 2001. Bone loss was detected in postmenopausal women and men. Free estradiol and SHBG predicted age-adjusted bone loss in postmenopausal women, but only free estradiol was associated after further adjustment for body mass index and smoking in mixed models (P < 0.05). After same adjustment, only SHBG persisted as a significant independent predictor of bone loss in men (P < 0.001). However, only 1% of the variance in bone loss was accounted for by these measurements. We therefore conclude that the relations between sex steroids and bone loss are weak and measurements of sex steroids are unlikely to assist in clinical decision making.     

Polymorphisms in the CYP19 and AR Genes—Relation to Bone Mass and Longitudinal Bone Changes in Postmenopausal Women With or Without Hormone Replacement Therapy: The Danish Osteoporosis Prevention Study

Polymorphisms in the androgen receptor ( AR) gene and genes encoding enzymes involved in synthesis of sex steroids (e.g., the CYP19 gene encoding aromatase) have recently received attention in osteoporosis research. In the Danish Osteoporosis Prevention Study, recent postmenopausal women were allocated to either hormone replacement therapy (HRT) or no treatment. We genotyped 1792 women for the CYP19 (TTTA)(n) repeat [short (TTTA)(n 7)] the CYP19 C(1558)-T, and the AR (CAG)(n) repeat polymorphism [short (CAG)(n < 22), long (CAG)(n >or= 22)], and investigated associations with bone mineral density (BMD) and 5-year change in BMD. The CYP19 polymorphisms were in strong linkage disequilibrium. Perimenopausal bone mass or bone loss in untreated women was not associated with the CYP19 polymorphisms. In hormone-treated women, BMD increase in the femoral neck was highest (+0.3%/year) for long CYP19 alleles, lowest (-0.09%/year) for short alleles, and intermediate (-0.002%/year) in heterozygous women, P = 0.015. Differences were also significant in the lumbar spine, total hip, and ultradistal forearm. The C(1558)-T T-allele was associated with a more pronounced response to HRT ( P = 0.04, total hip). AR genotype was not related to BMD, but a modifying effect of sex hormone-binding globulin (SHBG) was present. In the highest SHBG quartile (SHBG > 95 nmol/1, n = 222), AR genotype was associated with baseline BMD (femoral neck: P < 0.001, total hip: P = 0.008), but without a clear gene dosage effect. We have demonstrated that polymorphisms in the CYP19 gene are associated with the magnitude of bone gain in response to HRT and that the (CAG)(n) repeat polymorphism in the AR gene is associated with bone mass in women with high levels of SHBG. These findings emphasize the complexity of the genetics of bone mass and bone loss.     

Do Men and Women Fracture Bones at Similar Bone Densities?

When the World Health Organization (WHO) guidelines for the definition of osteoporosis in postmenopausal women were identified similar proposals were not developed for men as there was insufficient evidence about the relationship between bone density and fracture in men. We have therefore examined the relationship between bone density and vertebral fracture in men and women attending for assessment of possible osteoporosis. Two hundred and sixty-four women (age 64 [SD 10] years) and 37 men (age 55 [10] years) were studied. Bone density was measured in the lumbar spine and femoral neck by dual-energy X-ray absorptiometry and expressed both as bone mineral density (BMD; g/cm²) and as T-scores. In both sexes there was a sigmoid relationship between the cumulative frequency of vertebral fracture and bone density at both sites. There was a linear relationship between the log odds of fracture and bone mass for both sexes and both sites (r= 0.97–0.99; p<0.0001). The slope of these lines was significantly steeper for men than women. The BMD at which there was 50% risk of fracture was higher in men than women (0.908 vs 0.844 g/cm²). The difference between the slopes was similar when the bone mass was expressed as a T-score. However, the T-score associated with 50% prevalence of fracture was similar in the two sexes (F: −2.77 vs M: −2.60). We conclude that although there is a different relationship between bone density and fracture in the two sexes the current WHO definition of osteoporosis in postmenopausal women can be appropriately applied to men. Received: 24 February 1999 / Accepted: 12 July 1999