Cardiovascular disease and cancer are the leading causes of death in the United States, and hormone-dependent cancers (breast and prostate cancer) are the most common noncutaneous malignancies in women and men, respectively. The hormonal (endocrine-related) therapies that serve as a backbone for treatment of both cancers improve survival but also increase cardiovascular morbidity and mortality among survivors. This consensus statement describes the risks associated with specific hormonal therapies used to treat breast and prostate cancer and provides an evidence-based approach to prevent and detect adverse cardiovascular outcomes. Areas of uncertainty are highlighted, including the cardiovascular effects of different durations of hormonal therapy, the cardiovascular risks associated with combinations of newer generations of more intensive hormonal treatments, and the specific cardiovascular risks that affect individuals of various races/ethnicities. Finally, there is an emphasis on the use of a multidisciplinary approach to the implementation of lifestyle and pharmacological strategies for management and risk reduction both during and after active treatment.

Purpose of review To discuss current literature and hypotheses pertaining to the pathophysiology of increased bone fragility and fracture in men and women with type 2 diabetes mellitus. Recent findings Despite high bone mineral density, studies have shown that men and women with type 2 diabetes mellitus (T2DM) are at increased risk for fracture. Complications of T2DM including retinopathy and autonomic dysfunction may contribute to bone fracture by increasing fall risk. Nephropathy may lead to renal osteodystrophy. Lean mass and potentially fat mass, may additionally contribute to skeletal health in diabetes. There is increasing acknowledgement that the marrow microenvironment is critical to efficient bone remodeling. Medications including thiazolidinediones and selective serotonin reuptake inhibitors may also impair bone remodeling by acting on mesenchymal stem cell differentiation and osteoblastogenesis. T2DM is associated with significant alterations in systemic inflammation, advanced glycation end-product accumulation and reactive oxygen species generation. These systemic changes may also directly and adversely impact the remodeling cycle and lead to bone fragility in T2DM, though more research is needed. Summary Fracture is a devastating event with dismal health consequences. Identifying the extrinsic and intrinsic biochemical causes of bone fracture in T2DM will speed the discovery of effective strategies for fracture prevention and treatment in this at-risk population.

The dietary acid load created by the typical Western diet may adversely impact the skeleton by disrupting calcium metabolism. Whether neutralizing dietary acid with alkaline potassium salts results in sustained improvements in calcium balance remains controversial. In this randomized, double blind, placebo controlled study, 52 men and women (mean age 65.2 + 6.2 years) were randomly assigned to potassium citrate 60 mmol, 90 mmol or placebo daily with measurements of bone turnover markers, net acid excretion, and calcium metabolism including intestinal fractional calcium absorption and calcium balance obtained at baseline and six months. At six months, net acid excretion was significantly lower in both treatment groups compared to placebo and negative, meaning subjects’ dietary acid was completely neutralized (−11.3 mmol/day, 60 mmol/day; −29.5 mmol/day, 90 mmol/day, P < 0.001 compared to placebo). At 6-months, 24-hour urine calcium was significantly reduced in persons taking potassium citrate 60 mmol (−46 ± 15.9 mg/day) and 90 mmol (−59 ± 31.6 mg/day) daily compared with placebo (p<0.01). Fractional calcium absorption was not changed by potassium citrate supplementation. Net calcium balance was significantly improved in participants taking potassium citrate 90 mmol/day compared to placebo (142 ± 80 mg/day, 90 mmol vs. −80 ± 54 mg/day, placebo; p = 0.02). Calcium balance was also improved on potassium citrate 60 mmol/day, but this did not reach statistical significance (p=0.18). Serum C-telopeptide decreased significantly in both potassium citrate groups compared to placebo (−34.6 ± 39.1 ng/L, 90 mmol/d, p=0.05; −71.6 ± 40.7 ng/L, 60 mmol/day, p=0.02) while bone specific alkaline phosphatase did not change. Intact parathyroid hormone was significantly decreased in the 90 mmol/day group (p=0.01). Readily available, safe, and easily administered in an oral form, potassium citrate has the potential to improve skeletal health. Longer term trials with definitive outcomes such as bone density and fracture are needed.