Bisphosphonates and bone mineral density in patients with end-stage kidney disease and renal transplants: A 15-year single-centre experience.

Chronic Kidney Disease Stage 5 (CKD-5) imparts a 4-fold increase in minimal trauma fracture with a substantial increase in mortality following hip fracture. Bone disease in CKD is complex, characterised by abnormal levels of PTH, calcium, phosphate, ALP, and vitamin D, manifesting as a condition known as CKD-Mineral and Bone Disorder (CKD-MBD). While bisphosphonates (BPs) are widely used in the management of osteoporosis, their therapeutic role when end-stage renal function and bone disease co-exist remains unclear. This 15-year retrospective cohort study examines the long-term use of BPs in CKD-4 and -5 patients receiving no renal replacement therapy, haemodialysis and renal transplant in a tertiary centre in Sydney, Australia. In multivariate regression adjusting for age, baseline bone mineral density (BMD) and history of fracture, BP use was associated with net gain in lumbar spine bone density in renal transplant recipients over a mean treatment period of 3.5 years (net annual BMD gain of 0.039 g/cm2, p = 0.005). No such benefit was seen in hip BMD in CKD subjects. Regardless of transplant status, CKD patients treated with BPs had no improvement in hip BMD with a general decline in hip BMD across both groups during the study period (hip BMD: transplant recipients decline 0.024 ± 0.81 g/cm2, non-transplant CKD patients decline 0.055 ± 0.84 g/cm2). BP therapy did not result in significant changes in biochemical parameters (ALP, PTH, and phosphate) and no serious adverse effects were detected in association with BP use. In particular, kidney function was not affected by BPs post-transplant (eGFR = 43 ± 29 ml/min/1.73 m2, p = 0.80). BPs preserved lumbar spine bone density in kidney transplant recipients but did not prevent declines in hip bone mineral density in either transplant patients or those with CKD-4 and -5. Summary: There remains a lack of clarity of the risks vs. benefits of bone-sparing pharmacotherapy in chronic kidney disease Stages 4 and 5. This single-centre 15-year retrospective data analysis showed that bisphosphonates are not associated with any detectable serious adverse effects in CKD-4 and -5 and effective at mitigating lumbar spine bone loss in kidney transplant patients.

The Sydney AFF Score: A Simple Tool to Distinguish Females Presenting With Atypical Femur Fractures Versus Typical Femur Fractures.

Atypical femur fractures (AFF) are a rare but serious complication of long-term bisphosphonate use. Although clearly defined by ASBMR criteria, a proportion of patients with AFFs may go unrecognized and the use of qualitative fracture criteria may lead to uncertainty in AFF diagnosis, with significant therapeutic implications. A score that rapidly and accurately identifies AFFs among subtrochanteric femur fractures using quantitative, measurable parameters is needed. In a retrospective cohort of 110 female patients presenting with AFFs or typical femur fractures (TFFs), multiple logistic regression and decision tree analysis were used to develop the Sydney AFF score. This score, based on demographic and femoral geometry variables, uses three dichotomized independent predictors and adds one point for each: (age ≤80 years) + (femoral neck width <37 mm) + (lateral cortical width at lesser trochanter ≥5 mm), (score, 0 to 3). In an independent validation set of 53 female patients at a different centre in Sydney, a score ≥2 demonstrated 73.3% sensitivity and 69.6% specificity for AFF (area under the receiver-operating characteristic curve [AUC] 0.775, SE 0.063) and remained independently associated with AFF after adjustment for bisphosphonate use. The Sydney AFF score provides a quantitative means of flagging female patients with atraumatic femur fractures who have sustained an AFF as opposed to a TFF. This distinction has clear management implications and may augment current ASBMR diagnostic criteria. © 2021 American Society for Bone and Mineral Research (ASBMR).

Prevention of osteoporosis as a consequence of aromatase inhibitor therapy in postmenopausal women with early breast cancer: rationale and design of a randomized controlled trial.

BACKGROUND: Aromatase inhibitors (AIs) have improved the prognosis for breast cancer survivors and are now standard of care for postmenopausal women with hormone receptor positive early stage breast cancer. One side-effect, however, is a decrease in bone mineral density (BMD) and increased fracture risk. Since hormone replacement therapy (HRT) is contraindicated in these women, one prevention option is exercise combined with vitamin D and calcium. The effect of this intervention on drug-induced osteoporosis is unknown. METHODS: A single-blind randomized controlled trial will be undertaken to test the hypothesis that exercise combined with vitamin D and calcium can prevent the decrease in BMD associated with the use of AIs. Sixty postmenopausal women prescribed an AI for the treatment of breast cancer will be randomized into either an exercise or control group. Participants randomized to the exercise group will undertake a 12-month gym-based exercise program, 3 times per week involving resistance and impact training. Participants in the control group will be advised on the benefits of exercise for preventing osteoporosis, but not prescribed exercise. Both groups will receive vitamin D and calcium supplements. The primary outcome will be total hip bone mineral density measured via dual energy X-ray absorptiometry (DXA). Study outcomes will be compared between groups at baseline, 6months and 12months. SUMMARY: This study will investigate the effect of exercise in combination with vitamin D and calcium on prevention of drug-induced osteoporosis in postmenopausal women prescribed AIs for the treatment of breast cancer.