Abstract available in the Journal of Strength and Conditioning Research

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Hormone ablation therapy is a mainstay in the treatment of breast and prostate cancers. However, aromatase inhibitors (AIs) used in postmenopausal women with breast cancer and androgen-deprivation therapy (ADT) used in men with prostate cancer contribute to substantial bone loss, thereby increasing the risk of osteoporotic fractures. Evidence-based guidelines, therefore, urge oncology practices to screen these patients for bone loss and, if needed, provide treatment to maintain bone health. In addition to lifestyle modification and calcium or vitamin D supplementation, bone protection strategies include treatment with bisphosphonates and denosumab, a monoclonal antibody against RANK ligand. Identification of patients at greater risk for bone loss and fracture and proper interventions can reduce fracture rates. Oncology nurses can play an important role in screening these patients. The purpose of this article is to inform oncology nurses about the effects of cancer treatment on bone health, review current prevention and treatment options for cancer treatment-induced bone loss, and discuss recommendations for identifying high-risk individuals.

We quantified confidence intervals (CIs) for T-scores for the lumbar spine and hip and determined the practical effect (impact on diagnosis) of variability around the T-score cutpoint of -2.5. Using precision data from the literature for GE Lunar Prodigy dual-energy X-ray absorptiometry (DXA) systems, the 95% CI for the T-score was ±0.23 at the lumbar spine (L1-L4), ± 0.20 at the total hip, and ±0.41 at the femoral neck. Thus, T-score variations of ±0.23 or less at the spine, ±0.20 at the total hip, and ±0.41 at the femoral neck are not statistically significant. When diagnosing osteoporosis, T-scores in the interval -2.3 to -2.7 for spine or total hip (after rounding to conform to guidelines from the International Society for Clinical Densitometry) and -2.1 to -2.9 for femoral neck are not statistically different from -2.5. Better precision values resulted in smaller 95% CIs. This concept was applied to actual clinical data using Hologic DXA systems. The study cohort comprised 2388 white women with either normal or osteopenic spines in whom the densitometric diagnosis of osteoporosis would be determined by hip T-scores. When evaluating actual patient T-scores in the range -2.5 ± 95% CI, we found that the diagnosis was indeterminate in approximately 12% of women when T-scores for femoral neck were used and in 4% of women when T-scores for total hip were used, with uncertainty as to whether the classification was osteopenia or osteoporosis. We conclude that precision influences the variability around T-scores and that this variability affects the reliability of diagnostic classification.

Introduction: We determined the prevalence of left-right differences in hip bone mineral density (BMD) by dual-energy x-ray absorptiometry (DXA) and the resultant consequence, namely: the frequency at which patients would be classified differently if lumbar spine and only one hip (rather than both hips) were measured. Methods: This was a retrospective DXA scan reanalysis of 3012 white women ≥50 yrs who had scans of both hips using Hologic DXA systems. The difference between left and right hips was considered significant if it exceeded the least significant change (LSC) for any of three hip subregions (total hip, femoral neck, trochanter). The number of women with osteoporosis in both hips, the left hip only, or the right hip only was determined by lowest T-score from total hip, femoral neck, or trochanter. Results: Despite high left-right correlations of subregion BMD, significant left-right differences in BMD were common: the difference exceeded the LSC for 47% of women at total hip, 31% at femoral neck, and 56% at trochanter. Left-right differences in BMD that exceeded the LSC affected the percent agreement of left-right hip classification: for all women irrespective of spine status, there was 77% classification (diagnostic) agreement in hip pairs in which the left-right hip BMD difference exceeded the LSC versus 87% agreement in which LSC was not exceeded (significant difference in proportions, P<0.0001). The greatest risk of different classification would occur in women with normal spines as the diagnosis might be determined by hip T-scores. Using L1-4 lumbar spine T-scores, 1229 women were normal at the spine. Twenty-four (2%) were osteoporotic at both hips. However, 12 women (1%) were osteoporotic only in the left hip (significantly different from zero, P<0.001) and 11 (1%) only in the right hip (P<0.001); of these 23 women, the difference in BMD between the osteoporotic hip and the contralateral hip exceeded the LSC in 16 (70% of those with osteoporosis in only one hip). Using L1-4 lumbar spine T-scores, 1159 women were osteopenic at the spine. Of these, 126 (11%) were osteoporotic at both hips, 54 (5%) only in the left hip (P<0.001), and 42 (4%) only in the right hip (P<0.001); of these 96 women, the difference in BMD between the osteoporotic hip and the contralateral hip exceeded the LSC in 56 (58% of those with osteoporosis in only one hip). Conclusions: A statistically significant number of women with osteoporosis are potentially classified differently when scanning only one hip as a result of the high prevalence of left-right differences in BMD. Although the percentages are low, the total number of women affected may be large. From a public health perspective, the practice of scanning both hips could potentially identify more women with osteoporosis and may help prevent future hip fractures. © 2006 International Osteoporosis Foundation and National Osteoporosis Foundation.

The incidence of hypocalcemia and bone mineral density (BMD) changes in end-stage renal disease (ESRD) patients on denosumab remains unclear. We performed this meta-analysis to assess the incidence of denosumab-associated hypocalcemia and effects of denosumab on BMD in ESRD patients. A literature search was conducted using MEDLINE, EMBASE, and Cochrane Database from inception through November 2017 to identify studies evaluating incidence of denosumab-associated hypocalcemia and changes in serum calcium, phosphate, alkaline phosphatase (ALP), parathyroid hormone (PTH), and BMD from baseline to post-treatment course of denosumab in ESRD patients. Study results were pooled and analyzed using a random-effect model. The protocol for this meta-analysis is registered with PROSPERO (International Prospective Register of Systematic Reviews; no. CRD42017081074). Six observational studies with a total of 84 ESRD patients were enrolled. The pooled estimated incidence of hypocalcemia during denosumab treatment was 42% (95% CI 29–55%, I2 = 0%). Hypocalcemia occurred approximately 7 to 20 days after the first dose and reached nadir of low calcium levels in the first 2 weeks up to 2 months. However, there were no significant changes in serum calcium or phosphate from baseline to post-treatment course (≥ 3 months after treatment) with mean differences [MDs] of 0.20 mg/dL (95% CI, − 0.30 to 0.69 mg/dL) and − 0.10 mg/dL (95% CI, − 0.70 to 0.49 mg/dL). There were significant reductions in ALP and PTH levels with standardized mean differences (SMDs) of − 0.65 (95% CI − 1.13 to − 0.16) and − 1.89 (95% CI − 3.44 to − 0.34), respectively. There were significant increases in T-scores with MDs of 0.39 (95% CI 0.10 to 0.69) and 0.79 (95% CI 0.60 to 0.98) for lumbar spine and femoral neck, respectively. Our study demonstrates the estimated incidence of denosumab-associated hypocalcemia in dialysis patients of 42%. From baseline to post-treatment course, although there are no differences in serum calcium and phosphate, our findings suggest significant reductions in ALP and PTH and a significant increase in BMD. Currently, denosumab should not be considered as the treatment of choice in ESRD patients until more safety and efficacy data are available.

The purpose of this randomized controlled trial was to investigate temporal skeletal responses to short-term high intensity physical activity. Twenty-eight normal active females [age: 20.7 +/- 2.1 yr (mean +/- SD)] were randomized into exercise (EX, n = 15) or control (CN, n = 13) groups. The exercise group trained 6 days/wk for 6 wk, which consisted of maximal isokinetic knee flexion/extension 3 days/wk, combined with 3 days/wk running. The purpose was to expose the tibiae to a period of abruptly increased loading forces. Tibial bending stiffness (EIMRTA), and serum concentrations of biochemical markers of bone formation [osteocalcin (OC)], and bone resorption [n-telopeptide of type I collagen (NTx)] were measured at baseline, 2 wks, 4 wks, and 6 wks. Isokinetic concentric knee extension/flexion peak torque, as well as total body and site-specific bone mineral density (BMD) were measured at baseline and 6 wk. After training, the exercise group significantly increased (p < 0.05) isokinetic concentric peak torque for the dominant (13.6%) and non-dominant (5.7%) quadriceps, as well as dominant (7.7%) and non-dominant (9.5%) hamstrings, compared to the controls. No differences for total body or site-specific BMD were noted. A two-way multivariate repeated measures ANOVA revealed no timeâ ¢group interactions for composite tibial bending stiffness [(EIMRTA); p = 0.57] or the biochemical markers of bone turnover [(OC and NTx); p = 0.15] across the four sampling periods. While there were no main effects for group, a trend for time (p = 0.051) for composite EIMRTA was observed. The exercise group demonstrated a 20% increase in EIMRTA from baseline (74.8 +/- 22.3 Nm2) to 6 wk (89.8 +/- 24 Nm2), compared to controls who demonstrated a 4% increase (Baseline 86.5 +/- 23.8 Nm2; 6 wk 90 +/- 23.7 Nm2). Significant group differences (p = 0.05) were noted for OC, but not NTx. Differences (p < 0.05) for OC were observed at baseline [13.2 +/- 2.4 ng/ml (CN), 15.6 +/- 2.7 ng/ml (EX)], and follow-up ANCOVA revealed no differences for subsequent sampling periods. Main effects for time were found for OC and NTx (p < 0.001). Main effects for time in OC were attributable to changes in the exercise group (p < 0.01) and NTx (p < 0.01), but not the control group. / Ph. D.

Background: Lithium is the most effective long-term treatment for bipolar disease. It has, however,been associated with hypercalcemia and hyperparathyroidism. The aim of the study is to research howlithium associated hyperparathyroidism(LHPT)affects bone mineral density. Method: A sub-analysis was performed on an ongoing randomized prospective study evaluating the operation results from parathyroidectomy versus watchful waiting in 22patients with LHPT. The patients were followed-up for 2 years and their blood samples, bone mineral density (BMD) and FRAX assessment were analysed. The data from LHPT patients was also compared to a separate group of patients with primary hyperparathyroidism (PHPT) corresponding in age.Results: In comparing LHPT patients with PHPT apparent differences in the biochemical profile were detected, including elevated values of ionized Ca in PHPT (p=0.001), lower excretion of 24h urinary calcium in LHPT (p=0.003) and significantly higher values of PTH excretion in PHPT. LHPT showed tendencies to having better BMD (p=0.176). At 2-year follow-up of 8 LHPT patients, biochemicalvalues improved, suggesting cure, including lower risks of skeletal fractures. Discussion: The biochemical features in LHPT are distinctive from PHPT. However, each case is unique, and thebiochemicalvariety issimilar to PHPT. Confounding factors include age, sex, renal function and stability of the bipolar condition. Conclusions:The present study illustratesthat LHPT differs biochemically from PHPT. In comparison to PHPT, LHPT patients tend to have reduced BMD and the present study could not confirm the previous postulation that lithium could be protective of the skeleton. In conclusion, casesof LHPT should be assessed individually, since the clinical course is diverse. In patients risking fracture, parathyroidectomy should be considered.

Background: Lithium is the most effective long-term treatment for bipolar disease. It has, however,been associated with hypercalcemia and hyperparathyroidism. The aim of the study is to research howlithium associated hyperparathyroidism(LHPT)affects bone mineral density. Method: A sub-analysis was performed on an ongoing randomized prospective study evaluating the operation results from parathyroidectomy versus watchful waiting in 22patients with LHPT. The patients were followed-up for 2 years and their blood samples, bone mineral density (BMD) and FRAX assessment were analysed. The data from LHPT patients was also compared to a separate group of patients with primary hyperparathyroidism (PHPT) corresponding in age.Results: In comparing LHPT patients with PHPT apparent differences in the biochemical profile were detected, including elevated values of ionized Ca in PHPT (p=0.001), lower excretion of 24h urinary calcium in LHPT (p=0.003) and significantly higher values of PTH excretion in PHPT. LHPT showed tendencies to having better BMD (p=0.176). At 2-year follow-up of 8 LHPT patients, biochemicalvalues improved, suggesting cure, including lower risks of skeletal fractures. Discussion: The biochemical features in LHPT are distinctive from PHPT. However, each case is unique, and thebiochemicalvariety issimilar to PHPT. Confounding factors include age, sex, renal function and stability of the bipolar condition. Conclusions:The present study illustratesthat LHPT differs biochemically from PHPT. In comparison to PHPT, LHPT patients tend to have reduced BMD and the present study could not confirm the previous postulation that lithium could be protective of the skeleton. In conclusion, casesof LHPT should be assessed individually, since the clinical course is diverse. In patients risking fracture, parathyroidectomy should be considered.

Final publication is avilable at http://www.sciencedirect.com/science/article/pii/S0954611115300172 / 京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第19577号 / 医博第4084号 / 新制||医||1013(附属図書館) / 32613 / 京都大学大学院医学研究科医学専攻 / (主査)教授 伊達 洋至, 教授 平家 俊男, 教授 松田 秀一 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM