Hip fracture predicts subsequent hip fracture: a retrospective observational study to support a call to early hip fracture prevention efforts in post-fracture patients.

In this real-world retrospective cohort, subsequent hip fracture occurred in one in four patients with any initial fracture, most often after hip fracture, on average within 1.5 years. These data support the need for early post-fracture interventions to help reduce imminent hip fracture risk and high societal and humanistic costs. PURPOSE: This large retrospective cohort study aimed to provide hip fracture data, in the context of other fractures, to help inform efforts related to hip fracture prevention focusing on post-fracture patients. METHODS: A cohort of 115,776 patients (72.3% female) aged > 65 (median age 81) with an index fracture occurring at skeletal sites related to age-related bone loss between January 1, 2011, and March 31, 2015, was identified using health services data from Ontario, Canada, and followed until March 31, 2017. RESULTS: Hip fracture was the most common second fracture (27.8%), occurring in ≥ 19% of cases after each index fracture site and most frequently (33.0%) after hip index fracture. Median time to a second fracture of the hip was ~ 1.5 years post-index event. Patients with index hip fracture contributed the most to fracture-related initial surgeries (64.1%) and post-surgery complications (71.9%) and had the second-highest total mean healthcare cost per patient in the first year after index fracture ($62,793 ± 44,438). One-year mortality (any cause) after index hip fracture was 26.2% vs. 15.9% in the entire cohort, and 25.9% after second hip fracture. CONCLUSION: A second fracture at the hip was observed in one in four patients after any index fracture and in one in three patients with an index hip fracture, on average within 1.5 years. Index hip fracture was associated with high mortality and post-surgery complication rates and healthcare costs relative to other fractures. These data support focusing on early hip fracture prevention efforts in post-fracture patients.

Mortality in older adults following a fragility fracture: real-world retrospective matched-cohort study in Ontario.

BACKGROUND: Recent studies are lacking reports on mortality after non-hip fractures in adults aged > 65. METHODS: This retrospective, matched-cohort study used de-identified health services data from the publicly funded healthcare system in Ontario, Canada, contained in the ICES Data Repository. Patients aged 66 years and older with an index fragility fracture occurring at any osteoporotic site between 2011 and 2015 were identified from acute hospital admissions, emergency and ambulatory care using International Classification of Diseases (ICD)-10 codes and data were analyzed until 2017. Thus, follow-up ranged from 2 years to 6 years. Patients were excluded if they presented with an index fracture occurring at a non-osteoporotic fracture site, their index fracture was associated with a trauma code, or they experienced a previous fracture within 5 years prior to their index fracture. This fracture cohort was matched 1:1 to controls within a non-fracture cohort by date, sex, age, geography and comorbidities. All-cause mortality risk was assessed. RESULTS: The survival probability for up to 6 years post-fracture was significantly reduced for the fracture cohort vs matched non-fracture controls (p < 0.0001; n = 101,773 per cohort), with the sharpest decline occurring within the first-year post-fracture. Crude relative risk of mortality (95% confidence interval) within 1-year post-fracture was 2.47 (2.38-2.56) in women and 3.22 (3.06-3.40) in men. In the fracture vs non-fracture cohort, the absolute mortality risk within one year after a fragility fracture occurring at any site was 12.5% vs 5.1% in women and 19.5% vs 6.0% in men. The absolute mortality risk within one year after a fragility fracture occurring at a non-hip vs hip site was 9.4% vs 21.5% in women and 14.4% vs 32.3% in men. CONCLUSIONS: In this real-world cohort aged > 65 years, a fragility fracture occurring at any site was associated with reduced survival for up to 6 years post-fracture. The greatest reduction in survival occurred within the first-year post-fracture, where mortality risk more than doubled and deaths were observed in 1 in 11 women and 1 in 7 men following a non-hip fracture and in 1 in 5 women and 1 in 3 men following a hip fracture.

Fragility fracture identifies patients at imminent risk for subsequent fracture: real-world retrospective database study in Ontario, Canada.

BACKGROUND: The secondary fracture prevention gap in the osteoporosis field has been previously described as a 'crisis'. Closing this gap is increasingly important in the context of accumulating evidence showing that an incident fragility fracture is associated with an increased risk of subsequent fracture within 1-2 years, known as imminent fracture risk. The objective of this study was to use health services data to characterize the time between index fragility fractures occurring at different osteoporotic sites and subsequent fractures. METHODS: This retrospective observational study used de-identified health services data from the publicly funded healthcare system in Ontario, the largest province of Canada. Patients aged > 65 with an index fragility fracture occurring between 2011 and 2015 were identified from the ICES Data Repository using International Classification of Diseases (ICD)-10 codes. We examined median time to subsequent fragility fractures for osteoporotic fracture sites until the end of follow-up (2017). BMD assessment and use of osteoporosis therapies following index fracture were also characterized. RESULTS: Among 115,776 patients with an index fragility fracture, 17.8% incurred a second fragility fracture. Median time between index and second fracture occurring at any site was 555 days (interquartile range: 236-955). For each index fracture site examined, median time from index to second fracture was < 2 years. The proportion of patients with BMD assessment was 10.3% ≤1 year prior to and 16.4% ≤1 year post index fracture. The proportion of patients receiving osteoporosis therapy was 29.8% ≤1 year prior, 34.6% ≤1 year post, and 25.9% > 3 years post index fracture. CONCLUSIONS: This cohort of Canadian patients aged > 65 years who experienced a fragility fracture at any site are at imminent risk of experiencing subsequent fracture within the next 2 years and should be proactively assessed and treated.

Effect of whole-body vibration on calcaneal quantitative ultrasound measurements in postmenopausal women: a randomized controlled trial.

The purpose of this study was to examine the effect of whole-body vibration (WBV) on calcaneal quantitative ultrasound (QUS) measurements; which has rarely been examined. We conducted a single-centre, 12-month, randomized controlled trial. 202 postmenopausal women with BMD T score between -1.0 and -2.5, not receiving bone medications, were asked to stand on a 0.3 g WBV platform oscillating at either 90- or 30-Hz for 20 consecutive minutes daily, or to serve as controls. Calcium and vitamin D was provided to all participants. Calcaneal broadband attenuation (BUA), speed of sound, and QUS index were obtained as pre-specified secondary endpoints at baseline and 12 months by using a Hologic Sahara Clinical Bone Sonometer. 12-months of WBV did not improve QUS parameters in any of our analyses. While most of our analyses showed no statistical differences between the WBV groups and the control group, mean calcaneal BUA decreased in the 90-Hz (-0.4 [95% CI -1.9 to 1.2] dB MHz(-1)) and 30-Hz (-0.7 [95% CI -2.3 to 0.8] dB MHz(-1)) WBV groups and increased in the control group (1.3 [95% CI 0.0-2.6] dB MHz(-1)). Decreases in BUA in the 90-, 30-Hz or combined WBV groups were statistically different from the control group in a few of the analyses including all randomized participants, as well as in analyses excluding participants who had missing QUS measurement and those who initiated hormone therapy or were <80% adherent. Although there are consistent trends, not all analyses reached statistical significance. 0.3 g WBV at 90 or 30 Hz prescribed for 20 min daily for 12 months did not improve any QUS parameters, but instead resulted in a statistically significant, yet small, decrease in calcaneal BUA in postmenopausal women in several analyses. These unexpected findings require further investigation.

Effect of 12 months of whole-body vibration therapy on bone density and structure in postmenopausal women: a randomized trial.

BACKGROUND: Although data from studies in animals demonstrated beneficial effects of whole-body vibration (WBV) therapy on bone, clinical trials in postmenopausal women showed conflicting results. OBJECTIVE: To determine whether WBV improves bone density and structure. DESIGN: A 12-month, single-center, superiority, randomized, controlled trial with 3 parallel groups. (ClinicalTrials.gov registration number: NCT00420940) SETTING: Toronto General Hospital, Ontario, Canada. PARTICIPANTS: 202 healthy postmenopausal women with bone mineral density (BMD) T-scores between -1.0 and -2.5 who were not receiving prescription bone medications. INTERVENTION: Participants were randomly assigned to 1 of 3 groups (1:1:1 ratio) by using a block-randomization scheme and sealed envelopes. They were asked to stand on a low-magnitude (0.3g) 90-Hz or 30-Hz WBV platform for 20 minutes daily or to serve as control participants; all participants received calcium and vitamin D. MEASUREMENTS: Bone outcome assessors, who were blinded to group assignment, determined trabecular volumetric BMD and other measurements of the distal tibia and distal radius with high-resolution peripheral quantitative computed tomography and areal BMD with dual-energy x-ray absorptiometry at baseline and at 12 months. RESULTS: 12 months of WBV therapy had no significant effect on any bone outcomes compared with no WBV therapy. For the primary outcome of tibial trabecular volumetric BMD, mean change from baseline was 0.4 mg/cm(3) (95% CI, -0.4 to 1.2 mg/cm(3)) in the 90-Hz WBV group, -0.1 mg/cm(3) (CI, -1.0 to 0.8 mg/cm(3)) in the 30-Hz WBV group, and -0.2 mg/cm(3) (CI, -1.1 to 0.6 mg/cm(3)) in the control group (P = 0.55). Changes in areal BMD at the femoral neck, total hip, and lumbar spine were also similar among the groups. Overall, low-magnitude WBV at both 90 and 30 Hz was well-tolerated. LIMITATIONS: Adherence to WBV ranged from 65% to 79%. Double-blinding was not possible. CONCLUSION: Whole-body vibration therapy at 0.3g and 90 or 30 Hz for 12 months did not alter BMD or bone structure in postmenopausal women who received calcium and vitamin D supplementation.

A retrospective observational study of osteoporosis management after a fragility fracture in primary care.

In many countries, osteoporosis is predominantly managed by primary care physicians; however, management after a fragility fracture has not been widely investigated. We describe osteoporosis care gaps in a real-world patient cohort. Our findings help inform initiatives to identify and overcome obstacles to effective management of patients after fragility fracture. PURPOSE: A fragility fracture is a major risk factor for subsequent fracture in adults aged ≥ 50 years. This retrospective observational study aimed to characterize post-fracture management in Canadian primary care. METHODS: A total of 778 patients with an index fragility fracture (low-trauma, excluding small bones) occurring between 2014 and 2016 were identified from medical records at 76 primary care centers in Canada, with follow-up until January 2018. RESULTS: Of 778 patients (80.5% female, median age [IQR] 73 [64-80]), 215 were on osteoporosis treatment and 269 had osteoporosis diagnosis recorded prior to their index fracture. The median follow-up was 363 (IQR 91-808) days. Of patients not on osteoporosis treatment at their index fracture, 60.2% (n = 339/563) remained untreated after their index fracture and 62.2% (n = 23/37) continued untreated after their subsequent fracture. After their index fracture, fracture risk assessment (FRAX or CAROC) was not performed in 83.2% (n = 647/778) of patients, and 59.9% (n = 466/778) of patients did not receive bone mineral density testing. Of patients without osteoporosis diagnosis recorded prior to their index date, 61.3% (n = 300/489) remained undiagnosed after their index fracture. At least one subsequent fracture occurred in 11.5% (n = 86/778) of patients. CONCLUSION: In the primary care setting, fragility fracture infrequently resulted in osteoporosis treatment or fracture risk assessment, even after multiple fragility fractures. These results suggest a fragility fracture is not recognized as a major risk factor for subsequent fracture and its occurrence does not prompt primary care physicians to intervene. These data urge initiatives to identify and overcome obstacles to primary care physicians' effective management of patients after fragility fractures.

Effects of Whole-Body Vibration Therapy on Distal Tibial Myotendinous Density and Volume: A Randomized Controlled Trial in Postmenopausal Women.

Whole-body vibration (WBV) therapy has been proposed as a therapy to reduce sarcopenia and improve muscle strength. The purpose of this study was to explore whether 12 months of WBV therapy increases myotendinous density and volume of the distal tibia as measured by HR-pQCT in postmenopausal women in a parallel group, randomized controlled trial with 1:1:1 allocation to three arms. Postmenopausal women (N = 202) with low hip BMD were randomized to 20 min daily of 0.3g 30-Hz WBV therapy, 0.3g 90-Hz WBV therapy using the Juvent platform (Juvent, Somerset, NJ, USA), or no WBV. The main outcome measure was myotendinous density (HU) and volume (mm3) at the distal tibia measured at baseline and 12 months with HR-pQCT. There were no significant effects on myotendinous density or volume at the distal tibia after 12 months of daily 30- or 90-Hz WBV therapy compared with no WBV therapy. Mean change (SD) in myotendinous density from baseline was 4.6 (5.7) HU in the 30-Hz WBV group, 3.9 (6.1) HU in the 90-Hz WBV group, and 3.9 (5.4) HU in the control group (p = 0.70). Mean change (SD) in myotendinous volume from baseline was -7 (503) mm3 in the 30-Hz WBV group, 111 (615) mm3 in the 90-Hz WBV group, and 35 (615) mm3 in the control group (p = 0.50). In conclusion, WBV therapy at 30- or 90-Hz for 12 months had no significant effects on myotendinous density or volume at the distal tibia as measured by HR-pQCT in postmenopausal women. © 2018 The Authors. JBMR Plus Published by Wiley Periodicals, Inc. on behalf of the American Society for Bone and Mineral Research.

Assessment of the effect of strontium, lead, and aluminum in bone on dual-energy x-ray absorptiometry and quantitative ultrasound measurements: A phantom study.

PURPOSE: Dual-energy X-ray absorptiometry (DXA) is the gold standard technique to measure areal bone mineral density (aBMD) for the diagnosis of osteoporosis. Because DXA relies on the attenuation of photon to estimate aBMD, deposition of bone-seeking metallic elements such as strontium, lead, and aluminum that differ in atomic numbers from calcium can cause inaccurate estimation of aBMD. Quantitative ultrasound (QUS) is another technique available to assess bone health by measuring broadband ultrasound attenuation (BUA), speed of sound (SOS), and an empirically derived quantity called stiffness index (SI). Because the acoustic properties are not prone to significant change due to changes in microscopic atomic composition of bone, it is hypothesized that QUS is unaffected by the presence of bone-seeking elements in the bone. The objective of this study was to investigate the effect of strontium, lead, and aluminum on DXA-derived aBMD and QUS parameters using bone-mimicking phantoms compatible with both techniques. METHODS: Bone-mimicking phantoms were produced by homogeneously mixing finely powdered hydroxyapatite compounds that contain varying concentrations of strontium, lead, or aluminum with porcine gelatin solution. Seven strontium-substituted phantoms were produced with varying molar ratio of Sr/(Sr + Ca) ranging from 0% to 2%. Four lead-doped phantoms and four aluminum-doped phantoms were constructed with the respective analyte concentrations ranging from 50 to 200 ppm. An additional 0 ppm phantom was produced to be used as a baseline for the lead and aluminum phantom measurements. All phantoms had uniform volumetric bone mineral density (vBMD) of 200 mg/cm3 , and were assessed using a Hologic Horizon® DXA device and a Hologic Sahara® QUS device. Furthermore, theoretical aBMD bias for mol/mol% substitution of calcium with the three bone-seeking elements was calculated. RESULTS: Strong positive linear relationship was found between aBMD measured by DXA and strontium concentration (P < 0.001, r = 0.995). From the measurement of lead and aluminum phantoms using DXA, no statistically significant relationship was observed between aBMD and the analyte concentrations. For the QUS system, with an exception of BUA and lead concentration that exhibited statistically significant relationship (P < 0.038, r = 0.899), no statistically significant change was observed in all QUS parameters with respect to the clinically relevant concentration of all three elements. The calculated theoretical aBMD bias induced by 1 mol/mol% substitution of calcium with strontium, lead, and aluminum were 10.8%, 4.6%, and -0.7%, respectively. CONCLUSION: aBMD measured by DXA was prone to overestimation in the presence of strontium, but acoustic parameters measured by QUS are independent of strontium concentration. The deviation in aBMD induced by the clinically relevant concentrations of lead and aluminum under 200 ppm could not be detected using the Hologic Horizon® DXA device. Furthermore, the SI measured by the QUS system was not affected by lead or aluminum concentrations used in this study.

Phasic menstrual cycle effects on the control of breathing in healthy women.

This study examined the effects of menstrual cycle phase on ventilatory control. Fourteen eumenorrheic women were studied in the early follicular (FP; 1-6 days) and mid-luteal (LP; 20-24 days) phase of the menstrual cycle. Blood for the determination of arterial PCO(2) (PaCO(2)) , plasma strong ion difference ([SID]), progesterone ([P(4)]), and 17beta-estradiol ([E(2)]) concentrations were obtained at rest. Subjects performed a CO(2) rebreathing procedure that included prior hyperventilation and maintenance of iso-oxia to evaluate central and peripheral chemoreflex, and nonchemoreflex drives to breathe. Resting PaCO(2) and [SID] were lower; minute ventilation (V (E)), [P(4)] and [E(2)] were higher in the LP versus FP. Within the LP, significant correlations were observed for PaCO(2) with [P(4)], [E(2)] and [SID]. Menstrual cycle phase had no effect on the threshold or sensitivity of the central and/or peripheral ventilatory chemoreflex response to CO(2). Both (V (E)) and the ventilatory response to hypocapnia (representing nonchemoreflex drives to breathe) were approximately 1L/min greater in the LP versus FP accounting for the reduction in PaCO(2) . These data support the hypothesis that phasic menstrual cycle changes in PaCO(2) may be due, at least in part, to the stimulatory effects of [P(4)], [E(2)] and [SID] on ventilatory drive.

Effects of human pregnancy on the ventilatory chemoreflex response to carbon dioxide.

This study examined the effects of human pregnancy on the central chemoreflex control of breathing. Subjects were two groups (n=11) of pregnant subjects (PG, gestational age, 36.5+/-0.4 wk) and nonpregnant control subjects (CG), equated for mean age, body height, prepregnant body mass, parity, and aerobic fitness. All subjects performed a hyperoxic CO2 rebreathing procedure, which includes prior hyperventilation and maintenance of iso-oxia. Resting blood gases and plasma progesterone and estradiol concentrations were measured. During rebreathing trials, end-tidal Pco2 increased, whereas end-tidal Po2 was maintained at a constant hyperoxic level. The point at which ventilation (Ve) began to rise as end-tidal Pco2 increased was identified as the central chemoreflex ventilatory recruitment threshold for CO2 (VRTco2). Ve levels below (basal Ve) and above (central chemoreflex sensitivity) the VRTco2 were determined. The VRTco2 was significantly lower in the PG vs. CG (40.5+/-0.8 vs. 45.8+/-1.6 Torr), and both basal Ve (14.8+/-1.1 vs. 9.3+/-1.6 l/min) and central chemoreflex sensitivity (5.07+/-0.74 vs. 3.16+/-0.29 l.min-1.Torr-1) were significantly higher in the PG vs. CG. Pooled data from the two groups showed significant correlations for resting arterial Pco2 with basal Ve, central chemoreflex sensitivity, and the VRTco2. The VRTco2 was also correlated with progesterone and estradiol concentrations. These data support the hypothesis that pregnancy decreases the threshold and increases the sensitivity of the central chemoreflex response to CO2. These changes may be due to the effects of gestational hormones on chemoreflex and/or nonchemoreflex drives to breathe.