Physical activity and health-related quality of life among postmenopausal women with breast cancer treated with aromatase inhibitors.

PURPOSE: Breast cancer is the most common non-cutaneous cancer in women with an estimated 268,600 new cases diagnosed in 2019, joining the over 3 million women living with the disease. To reduce cancer recurrence, postmenopausal women (highest incidence and prevalence of breast cancer) who test positive for hormone receptors in their tumors are candidates for adjuvant endocrine therapy (i.e., aromatase inhibitors [AIs]). Despite the benefits of AIs in the treatment for breast cancer, many women remain at risk for complications, including osteoporosis and fractures, all of which can adversely affect health-related quality of life (HRQoL). Increased attention is being paid to the role physical activity (PA) may have in improving health outcomes in survivors of breast cancer, but few studies focus on postmenopausal women. We sought to examine (1) the percentage of women in our sample meeting (or not meeting) the American College of Sports Medicine (ACSM) PA recommendations, (2) the relationship between AI use and three types of PA (leisure time, strength training, and walking), and (3) the relationship between PA and HRQoL by AI use, controlling for covariates. METHODS: Postmenopausal women with breast cancer (n = 170), ages 50-95 years (M = 68.7), diagnosed with stage 1-3 disease, 45% on AIs, were recruited. Demographic, HRQoL, and PA data were collected via patient self-report, while clinical data (AI use) were abstracted from patient medical records. To address study aims, we utilized descriptive statistics, chi-square analyses, and multiple linear regressions, respectively. RESULTS: Half of the sample met the ACSM recommendations for total leisure-time PA (vigorous and moderate intensity combined), and 65.3% (n = 111) weekly walking. With regard to strength training, 36.5% of the women met these ACSM recommendations. Generally, there were positive relationships between AI use and most HRQoL domains. There were no statistically significant relationships between PA (meeting recommendations or not) and HRQoL by AI use. CONCLUSION: The proportion of women meeting guidelines for walking activity was encouraging. It is imperative that healthcare professionals providing care to breast cancer survivors follow up regarding symptoms, side effects, and physical activity in tandem to fully understand their relationship on an individual level.

Quality of life improves among post-menopausal women who received bone augmentation during dental implant therapy.

Quality of life outcomes among patients receiving implants have been well studied, but little is known about the effects of bone augmentation in this therapy. The purpose of this paper was to assess quality of life changes among postmenopausal women receiving dental implants with bone augmentation during implant therapy. This was a prospective cohort study. 48 patients were recruited at the University of Connecticut Health Center and received one of three surgical augmentation methods: dehiscence repair; expansion alone; or expansion with dehiscence repair. The predictor variable was type of augmentation procedure. Quality of life measured by the Oral Health Impact Profile-14 (OHIP-14) was the outcome measure and was assessed prior to treatment, 1 week, 8 weeks and 9 months after surgery. Changes in OHIP-14 were evaluated by repeated measures analysis of variance. The mean initial OHIP-14 scores on total items checked were 4.6 (SD=3.0) and declined significantly to 2.0 (SD=2.0) at 9 months. The mean baseline severity score was 15.4 (SD=8.9) improving significantly to 7.5 (SD=7.6) at 9 months. Type of augmentation procedure did not affect quality of life. The participants' quality of life improved continuously from the pretreatment to the 9-month assessment, including improvements 1 week after implant placement.

Estradiol rapidly inhibits osteoclastogenesis and RANKL expression in bone marrow cultures in postmenopausal women: a pilot study.

UNLABELLED: We examined RANKL expression and OCL formation in cultured bone marrow cells from eight postmenopausal women in response to E(2). E(2) treatment inhibited the ability of hematopoietic cells to form OCLs in response to RANKL, and decreased RANKL production. These changes are likely involved in the ability of E(2) to influence the development of osteoporosis. INTRODUCTION: Estrogen (E(2)) deficiency at menopause increases osteoclast (OCL) formation and bone resorption, predisposing women to osteoporosis. We examined receptor activator of NF-kappa B-ligand (RANKL) expression and in vitro OCL formation in cultured bone marrow cells from eight postmenopausal women before and after 3 weeks of E(2) therapy and three untreated premenopausal women. METHODS: TRAP staining and resorption pit assay determined OCL number and function. Flow cytometry measured the distribution of marrow cell types and expression of RANKL in the macrophage-enriched fraction (R1) and a lymphocyte-enriched fraction (R2). RESULTS: RANKL (3-100 ng/ml) produced a dose-dependent increase in in vitro OC formation and E(2) therapy significantly (p < 0.01) inhibited OCL formation by 33 to 50%. A small proportion of marrow cells bound anti- RANKL Ab (0.2-4.3%). There was no effect of E(2) on the percentage of cells binding the anti-RANKL Ab in the R1 fraction. In the R2 fraction E(2) treatment decreased the percentage of cells binding anti-RANKL Ab by 68 +/- 9% (p < 0.01). CONCLUSION: Three weeks of E(2) treatment had a dual action. It inhibited the ability of hematopoietic cells to form OCLs in response to RANKL, and decreased the production of RANKL in cells of the bone marrow. The observed changes in the osteoclastic potential of bone marrow cells are likely involved in the ability of E(2) to regulate bone mass and influence the development of osteoporosis.

The effect of 6 months of androgen deprivation therapy on muscle and fat mass in older men with localized prostate cancer.

OBJECTIVE: To evaluate body composition changes, specifically skeletal muscle mass, in men receiving androgen deprivation with luteinizing-hormone releasing hormone-agonist (LHRH-A) for prostate cancer (PCa) in comparison with healthy controls. DESIGN: Retrospective analysis of body composition changes in men with prostate cancer receiving LHRH-A therapy from 2 clinical trials compared to men without prostate cancer serving as a placebo-control in another clinical trial. SETTING: Clinical Research Center in Connecticut. PARTICIPANTS: Thirty men (> 60 years) receiving 6 months of LHRH-A therapy for PCa were compared to a healthy group of 25 men without PCa. MEASUREMENTS: Appendicular skeletal muscle/height2 (ASM/ht2), lean and fat mass were assessed by dual energy x-ray absorptiometry. Total testosterone levels were assessed by enzyme immunoassay. RESULTS: At baseline, 12/30 (40%) of the treatment group and 7/25 (28%) of the control group (p = 0.11) met criteria for sarcopenia. There were no differences between control groups in ASM/ht2 or lean mass. The LHRH-A group had a higher percent body fat than the control group, 29.8 +/- 6.3 versus 26.3 +/- 4.6 (p = 0.02). ASM/ht2 and lean mass decreased in the LHRH-A group from 7.5 +/- 0.9 kg to 7.3 +/- 0.9 kg (-2.3% +/- 0.03; p < or = 0.001) and 53.5 +/- 5.4 kg to 52.3 +/- 5.3 kg (-2.1% +/- 0.03; p < or = 0.001), respectively. There was no muscle loss in the control group. At 6 months, the LHRH-A group had increased percent body fat from 29.8 +/- 6.4 to 32.2 +/- 5.8 (9.5% +/- 0.13; p < or = 0.001), whereas the control group had decreased in percent body fat from 26.6 +/- 4.6 to 25.3 +/- 5.0 (-3.8% +/- 0.08; p = 0.02). CONCLUSIONS: Men undergoing LHRH-A treatment for PCa decreased appendicular skeletal muscle and lean tissue and increased body fat within 6 months of initiation of therapy. Lifestyle changes or medical interventions to minimize the effects of androgen deprivation therapy for PCa deserve investigation.

The effect of aromatase inhibition on sex steroids, gonadotropins, and markers of bone turnover in older men.

There is evidence that estrogen decreases bone turnover in men as well as women. We therefore hypothesized that older men would show increased bone resorption in response to inhibition of the aromatase enzyme, which converts androgens to estrogen. Fifteen eugonadal men over 65 yr were treated for 9 weeks with 2.0 mg/day of anastrozole, an aromatase inhibitor. After 9 weeks of treatment, there were significant decreases in estradiol, estrone, and sex hormone-binding globulin levels by 29%, 73%, and 16%, respectively, and total testosterone increased significantly by 56%. Despite the limited decrease of estrogen and the increase in testosterone, C-telopeptide of type 1 collagen showed a progressive significant increase of 11%, 24%, and 33% (P for trend = 0.033) above baseline at 3, 6, and 9 weeks, respectively. N-telopeptide of type 1 collagen values were highly correlated with C-telopeptide of type 1 collagen, but the change in N-telopeptide of type 1 collagen was not statistically significant. Bone-specific alkaline phosphatase and N-terminal type I procollagen peptides showed significant decreases of 8% and 11% of baseline at 9 weeks. Osteocalcin decreased significantly by 30% at 18 weeks. We conclude that aromatase inhibition can reduce estrogen levels in older men, but this effect is limited, perhaps because of feedback stimulation of testosterone production, and that endogenous estrogen derived from aromatization of testosterone plays a role in bone metabolism of older men by limiting the rate of bone resorption.

The effect of short-term treatment with micronized estradiol on bone turnover and gonadotrophins in older men.

Evidence for the role of estrogen in male bone metabolism has been confirmed by studies on a man with a genetic defect in the estrogen receptor as well as men with aromatase defects. All exhibited tall stature, delayed epiphysial closure, decreased bone density and increased bone turnover. Estrogen is likely to affect bone turnover in men throughout life; therefore, we hypothesized that older men would show decreased bone resorption in response to estrogen therapy. To test our hypothesis, fourteen community-dwelling men with osteopenia of the femoral neck were treated for 9 weeks with micronized estradiol, 1 mg/d, a dose which is effective in postmenopausal women. Each subject served as his own control. Markers of bone resorption, N-terminal collagen crosslinks (NTX) and C-terminal collagen crosslinks (CTX) and markers of bone formation, osteocalcin (OC) and bone specific alkaline phosphatase (BSAP) were measured every 3 weeks during a 9-week treatment period and 9 weeks post-treatment. Sex hormones, gonadotrophins and calciotropic hormones were measured at baseline, 9 weeks on treatment and 9 weeks post- treatment. After 9 weeks of treatment, estradiol and estrone levels increased significantly by greater than 6-fold and 15-fold, respectively. SHBG levels increased significantly by 17%. Testosterone and free testosterone levels decreased significantly by 27% and 34%, respectively. Markers of bone resorption showed wide variation at baseline and while on treatment. There was no correlation between changes in bone markers and changes in estrogen levels. During treatment, 11 patients showed a decrease of NTX or CTX, but three showed an increase. These three and one other subject had high initial levels of FSH and LH, suggesting some degree of primary gonadal failure, which decreased during estrogen therapy. Thus, the change in NTX (and CTX) after 9 weeks of E2 treatment was correlated with initial FSH (r= -.66, p= .01) and LH (r= -.73, p= .003) values. In addition, the largest decrease in free testosterone at 9 weeks was correlated with the higher values for NTX, CTX and BAP (r=-0.66, -0.68, -0.70 respectively; p< or =.01 for each of the markers). Treatment was generally well tolerated. Side effects of treatment were minimal, and included breast tenderness and decreased libido which reversed after treatment. We conclude that it is feasible to give low dose estrogen to healthy older men, but that the effects on bone turnover are not consistent. Changes in central feedback and in endogenous sex hormone production may alter the response of bone turnover to exogenous estrogen in this population.

Differential diagnosis and secondary causes of osteoporosis.

Secondary osteoporosis refers to osteoporosis in which an underlying cause or factor other than those attributable to the postmenopausal state or aging can be identified. Primary, or idiopathic, osteoporosis implies that a secondary cause cannot be found. Secondary osteoporosis occurs not only in postmenopausal women but also in men and premenopausal women. In series reported from specialized centers, as many as 30% of postmenopausal women and 50% to 80% of men have an identifiable secondary cause of osteoporosis, although the frequency of secondary osteoporosis is probably much lower in the general population. In assessing the patient with osteoporosis, it is important to look for secondary causes and aggravating factors that are reversible and amenable to therapy. In addition to secondary forms, 2 metabolic bone diseases, osteomalacia and primary hyperparathyroidism, can mimic or aggravate osteoporosis. This paper will summarize the differential diagnosis and management of osteoporosis, osteomalacia, and hyperparathyroidism and review the most common causes of secondary osteoporosis.

Osteoporosis in older men.

Historically, the focus in osteoporosis has been on postmenopausal women. In the past few years, information about osteoporosis in other populations, including men, has begun to emerge. Although less common in older men, osteoporosis nonetheless represents a major health concern. Approximately 30% of hip fractures worldwide occur in men, resulting in significant mortality and loss of independence. The incidence of osteoporotic fractures in men is increasing. The reason for this is unclear, but improvement in longevity and better management of other chronic diseases most likely play a role. Two recent studies have addressed the question of fracture risk in men past middle age and have estimated that men > 50 years of age have a 19% to 25% lifelong risk of osteoporotic fracture. Mortality is higher following hip fracture and pain is more intense in men than in women following severe vertebral fracture.

Osteoporosis: detection, prevention, and treatment in primary care.

Osteoporosis is a silent disease that often remains asymptomatic and undetected until bone fracture occurs. Because of the high morbidity associated with fracture, prevention is a clinical priority. In order to identify those who would benefit from therapeutic intervention, bone density measurement is indicated in patients with risk factors for osteoporosis. Therapies include hormone replacement, calcitonin, bisphosphonates, and selective estrogen receptor modulators, as well as exercise and supplements of calcium and vitamin D. The goal of all treatments is to decrease the risk of fracture by minimizing bone loss and increasing bone mass.

Oral estrogen improves serum lipids, homocysteine and fibrinolysis in elderly men.

The effects of estrogen on cardiovascular risk factors have been less well defined in men than in women. We measured lipid and lipoprotein concentrations, lipoprotein particle size distributions, lipoprotein (a), homocysteine, and markers of thrombosis and fibrinolysis in 18 [corrected] healthy elderly men (age 74 +/- 3 years, mean +/- S.D.) before and after 9 weeks of treatment with 0.5, 1 or 2 mg/day of oral micronized 17beta-estradiol. LDL-C (-6%), apo B (-9%), triglyceride (-5%), and homocysteine (-11%) concentrations decreased with estradiol, whereas HDL-C (+14%) increased. Intermediate-size VLDL subclass concentrations were lowered and LDL and HDL subclass levels altered in such a way as to cause average LDL and HDL particle size to increase. Lipoprotein (a) did not change. Fibrinogen (-13%) and plasminogen activator inhibitor-1 (PAI-1) concentrations (-26%) decreased, but there were no changes in thrombotic markers including thrombin-antithrombin III complex, prothrombin fragment 1.2, D-dimer, antithrombin activity, protein-C and S and von Willebrand factor antigen. Breast tenderness occurred in four men and heartburn in five but did not require discontinuation of treatment. We conclude that oral estrogen in men reduces homocysteine, fibrinogen, and PAI-1 concentrations and favorably influences VLDL, LDL and HDL subclass levels without increasing markers of thrombotic risk.

Dexamethasone suppresses in vivo levels of bone collagen synthesis in neonatal mice.

The objective of this study was to determine the acute effects of glucocorticoids on in vivo levels of bone collagen synthesis in neonatal mice. Mice were injected with vehicle or dexamethasone at the start of the experiment. At 22 h, mice were given a 10 microCi injection of [3H]proline. At 24 h, the mice were sacrificed and the incorporation of [3H]proline into collagenase-digestible CDP labeling) and noncollagen (NCP labeling) protein in calvariae were determined by digestion with bacterial collagenase. Calvarial RNA was analyzed for COL 1A1 and osteocalcin mRNA levels by Northern blotting. After 24 h, vehicle-treated mice showed a 9.8 +/- 1.0% weight gain while dexamethasone-treated mice (1 mg/kg) had a 7.4 +/- 0.8% weight loss. Dexamethasone (1 mg/kg) decreased CDP and NCP labeling in calvariae by 51 +/- 4% and 17 +/- 4%, respectively (13 experiments). The inhibitory effect on protein labeling was selective for collagen since dexamethasone decreased the percent collagen synthesis from 25.4 +/- 1.6% to 16.6 +/- 1.0% (13 experiments). Dexamethasone at 3 mg/kg also decreased CDP labeling and the percent collagen synthesis in calvariae. There was a 30% reduction in COL1A1 mRNA levels and a 67% decrease in osteocalcin mRNA levels. To determine the reversibility of the inhibition of collagen synthesis, mice were given a single injection of dexamethasone (1 mg/kg) and then injected with [3H]proline 2 h prior to sacrifice at 24, 48, or 72 h. The reduction in CDP labeling observed at 24 h was fully reversed by 48-72 h. Moreover, by 72 h, the-rate of weight gain by dexamethasone-treated mice was similar to vehicle-treated controls. These data show that administration of dexamethasone to neonatal mice leads to a selective decrease in bone collagen synthesis within 24 h that is accompanied by down-regulation of osteocalcin and COL1A1 mRNA levels. This model will be useful in determining mechanisms by which high dose glucocorticoids inhibit bone formation in vivo.

Chiasmal herniation as a complication of bromocriptine therapy.

INTRODUCTION: Medical treatment of macroprolactinomas with dopamine agonists decreases tumor mass and improves visual defects. We report an unusual complication of a macroprolactinoma responding to bromocriptine: a visual field defect caused by downward herniation of the optic chiasm. MATERIALS AND METHODS: A 64-year-old woman was found to have a 4.5 cm macroprolactinoma with superior displacement of the optic chiasm, bitemporal hemianopia, and serum prolactin concentration (P) of 17,060 micrograms/L. Bromocriptine was initiated at 2.5 mg/day and increased to 7.5 mg/day over 2 months. RESULTS: After 2 months, visual fields improved significantly and tumor height decreased to 3 cm with resolution of the optic chiasm displacement. P decreased to 1,180 micrograms/L. After 5 months of therapy, visual fields were normal, and P was 8 micrograms/L. After 8 months of therapy, new bilateral visual defects were observed. Magnetic resonance imaging (MRI) revealed further decrease of the tumor height to 1.5 cm, and inferior and leftward traction of the optic chiasm as the probable mechanism for the new visual field deficit. P was < 1 microgram/L. Bromocriptine was decreased to 5 mg/day to allow reduced traction on the optic chiasm and its blood supply. Over the next 4 months, visual field abnormalities resolved. CONCLUSIONS: We report the development of a visual field abnormally that is explained by chiasmal herniation caused by a shrinking macroprolactinoma. This complication resolved with a decrease in the bromocriptine dose. We suggest that patients undergoing bromocriptine therapy for macroprolactinomas be followed for this potential complication.