Managers' experiences of providing end-of-life care under the Home Care Package Program.

OBJECTIVE: The study explored the experiences of Australian aged care providers in supporting clients on a home care package to die at home. METHODS: Semistructured interviews were conducted with 13 aged care managers responsible for delivering services under the Home Care Package Program. Interviews were analysed thematically. RESULTS: Four themes emerged that illuminated managers' experiences: struggling to meet a preference to die at home; lack of opportunities to build workforce capacity in end-of-life care; challenges in negotiating fragmented funding arrangements between health and aged care providers; and mixed success in collaborating across sectors. CONCLUSIONS: Aged care providers want to support older Australians who prefer to stay at home at the end of life. However, most clients are admitted to a residential facility when their care needs exceed a home care budget long before a specialist palliative care team will intervene. Budgets for health and aged care providers must be sufficient and flexible to support timely access to end-of-life care, to reward collaboration across sectors and to invest in building palliative care skills in the nursing and personal care workforce.

Older Aboriginal Australians' Health Concerns and Preferences for Healthy Ageing Programs.

While there is strong evidence of the need for healthy ageing programs for older Aboriginal Australians, few are available. It is important to understand older Aboriginal Australians' perspectives on healthy ageing in order to co-design culturally-appropriate programs, including views on technology use in this context. Semi-structured interviews were conducted with 34 Aboriginal Australians aged 50 years and older from regional and urban communities to explore participants' health concerns, preferences for healthy ageing programs, and receptiveness to technology. Qualitative data were analyzed using a grounded theory approach. This study found that older Aboriginal Australians are concerned about chronic health conditions, social and emotional well-being, and difficulties accessing health services. A range of barriers and enablers to participation in current health programs were identified. From the perspective of older Aboriginal people, a successful healthy ageing program model includes physical and cognitive activities, social interaction, and health education. The program model also provides culturally safe care and transport for access as well as family, community, cultural identity, and empowerment regarding ageing well as central tenets. Technology could also be a viable approach for program delivery. These findings can be applied in the implementation and evaluation of culturally-appropriate, healthy ageing programs with older Aboriginal people.

Staying in touch with the community: understanding self-reported health and research priorities in older Aboriginal Australians.

OBJECTIVES: Aboriginal Australians experience higher rates of non-communicable chronic disease, injury, dementia, and mortality than non-Aboriginal Australians. Self-reported health is a holistic measure and may fit well with Aboriginal views of health and well-being. This study aimed to identify predictors of self-reported health in older Aboriginal Australians and determine acceptable research methodologies for future aging research. DESIGN: Longitudinal, population-based study. SETTING: Five communities across New South Wales, Australia (two urban and three regional sites). PARTICIPANTS: Aboriginal and Torres Strait Islander people (n = 227; 60-88 years, M = 66.06, SD = 5.85; 145 female). MEASUREMENTS: Participants completed baseline (demographic, medical, cognitive, mental health, and social factors) and follow-up assessments (self-reported health quantified with 5-point scale; sharing thoughts on areas important for future research). Predictors of self-reported health were examined using logistic regression analyses. RESULTS: Self-reported health was associated with sex, activities of daily living, social activity participation, resilience, alcohol use, kidney problems, arthritis, falls, and recent hospitalization. Arthritis, kidney problems, and resilience remained significant in multiple logistic regression models. CONCLUSIONS: Perceived resilience and the absence of certain chronic age-related conditions predict older Aboriginal peoples' self-reported health. Understanding these factors could inform interventions to improve well-being. Findings on acceptable research methodologies suggest that many older Aboriginal people would embrace a range of methodologies within long-standing research partnerships, which is an important consideration for Indigenous population research internationally.

Factors Associated with the High Prevalence of Dementia in Older Aboriginal Australians.

Dementia prevalence in Aboriginal and Torres Strait Islander Australians is three to five times higher than the general Australian population. A better understanding of the underlying biomedical and social risk factors is needed to guide dementia prevention in Aboriginal Australians. The current study is the first to examine potential risk factors for dementia in the majority urban and regional population, with a representative sample of 336 Aboriginal Australians aged 60 years and older. Participants included 45 people with a dementia diagnosis (n = 27 probable/possible Alzheimer's disease); and 286 people without dementia. Univariate logistic regression analyses (controlling for age) identified childhood trauma, mid-life factors (history of unskilled work, past high-risk alcohol use), and medical factors (history of stroke, head injury with loss of consciousness, epilepsy) as risk factors for dementia. Multivariable analysis revealed age, childhood trauma, unskilled work, stroke, and head injury as independent predictors of all-cause dementia. A range of comorbid factors related to dementia was also identified (i.e., functional impairment, incontinence, recent hospital admission, low body mass index, living in residential care, depression, current high-risk alcohol use, social isolation, low physical activity levels). These findings extend previous outcomes in a remote Aboriginal population by highlighting that life-course social determinants of health, in addition to neurological disorders, likely play an important role in elevating dementia risk. Certain psychosocial and medical exposures are highly prevalent in Aboriginal Australians, similar to other indigenous populations, and should be considered when designing targeted and culturally appropriate prevention initiatives to reduce the burden of dementia.

The effectiveness of a sustained nurse home visiting intervention for Aboriginal infants compared with non-Aboriginal infants and with Aboriginal infants receiving usual child health care: a quasi-experimental trial - the Bulundidi Gudaga study.

BACKGROUND: In Australia there is commitment to developing interventions that will 'Close the Gap' between the health and welfare of Indigenous and non-Indigenous Australians and recognition that early childhood interventions offer the greatest potential for long term change. Nurse led sustained home visiting programs are considered an effective way to deliver a health and parenting service, however there is little international or Australian evidence that demonstrates the effectiveness of these programs for Aboriginal infants. This protocol describes the Bulundidi Gudaga Study, a quasi-experimental design, comparing three cohorts of families from the Macarthur region in south western Sydney to explore the effectiveness of the Maternal Early Childhood Sustained Home-visiting (MECSH) program for Aboriginal families. METHODS: Mothers were recruited when booking into the local hospital for perinatal care and families are followed up until child is age 4 years. Participants are from three distinct cohorts: Aboriginal MECSH intervention cohort (Group A), Non-Aboriginal MECSH intervention cohort (Group B) and Aboriginal non-intervention cohort (Group C). Eligible mothers were those identified as at risk during the Safe Start assessment conducted by antenatal clinic midwives. Mothers in Group A were eligible if they were pregnant with an Aboriginal infant. Mothers in Group B were eligible if they were pregnant with a non-Aboriginal infant. Mothers in Group C are part of the Gudaga descriptive cohort study and were recruited between October 2005 and May 2007. The difference in duration of breastfeeding, child body mass index, and child development outcomes at 18 months and 4 years of age will be measured as primary outcomes. We will also evaluate the intervention effect on secondary measures including: child dental health; the way the program is received; patterns of child health and illness; patterns of maternal health, health knowledge and behaviours; family and environmental conditions; and service usage for mothers and families. DISCUSSION: Involving local Aboriginal research and intervention staff and investing in established relationships between the research team and the local Aboriginal community is enabling this study to generate evidence regarding the effectiveness of interventions that are feasible to implement and sustainable in the context of Aboriginal communities and local service systems. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12616001721493 Registered 14 Dec 2016. Retrospectively registered.

The oral health behaviours and fluid consumption practices of young urban Aboriginal preschool children in south-western Sydney, New South Wales, Australia.

ISSUE ADDRESSED: Australian Aboriginal children have a higher risk of dental caries yet there is limited focus on oral health risk factors for urban Aboriginal preschool children. This study examined the oral health behaviours and fluid consumption practices of young children from an urban Aboriginal community in south-western Sydney, Australia. METHODS: In total, 157 Aboriginal children who were recruited to the "Gudaga" longitudinal birth cohort participated in this study. A survey design was employed and parents responded to the oral health questions when their child was between 18 and 60 months. RESULTS: Few parents (20%) were concerned about their child's oral health across the time period. By 60 months, only 20% of children had seen a dentist while 80% were brushing their teeth at least once daily. High levels of bottle use were seen up to 30 months. Consumption of sugary drinks was also very high in the early years, although this was replaced by water by 36 months. CONCLUSIONS: While there are some encouraging findings, such as the rates of tooth brushing and increasing rates of water consumption, the findings do highlight the poor uptake of dental services and high levels of bottle usage among urban aboriginal children during their early years. SO WHAT?: Targeted oral health promotional programs are needed in the urban Aboriginal community to better support parents understanding of good oral health practices in the early years and engagement with dental health services.

Childhood Stress and Adversity is Associated with Late-Life Dementia in Aboriginal Australians.

OBJECTIVES: High rates of dementia have been observed in Aboriginal Australians. This study aimed to describe childhood stress in older Aboriginal Australians and to examine associations with late-life health and dementia. DESIGN: A cross-sectional study with a representative sample of community-dwelling older Aboriginal Australians. SETTING: Urban and regional communities in New South Wales, Australia. PARTICIPANTS: 336 Aboriginal and/or Torres Strait Islander Australians aged 60-92 years, of whom 296 were included in the current analyses. MEASUREMENTS: Participants completed a life course survey of health, well-being, cognition, and social history including the Childhood Trauma Questionnaire (CTQ), with consensus diagnosis of dementia and Alzheimer disease. RESULTS: CTQ scores ranged from 25-117 (median: 29) and were associated with several adverse childhood indicators including separation from family, poor childhood health, frequent relocation, and growing up in a major city. Controlling for age, higher CTQ scores were associated with depression, anxiety, suicide attempt, dementia diagnosis, and, specifically, Alzheimer disease. The association between CTQ scores and dementia remained significant after controlling for depression and anxiety variables (OR: 1.61, 95% CI: 1.05-2.45). In contrast, there were no significant associations between CTQ scores and smoking, alcohol abuse, diabetes, or cardiovascular risk factors. CONCLUSIONS: Childhood stress appears to have a significant impact on emotional health and dementia for older Aboriginal Australians. The ongoing effects of childhood stress need to be recognized as people grow older, particularly in terms of dementia prevention and care, as well as in populations with greater exposure to childhood adversity, such as Aboriginal Australians.

Comparison of Three Cognitive Screening Tools in Older Urban and Regional Aboriginal Australians.

BACKGROUND: Validated cognitive screening tools for use in urban and regional Aboriginal populations in Australia are lacking. METHODS: In a cross-sectional community-based study, 235 participants were assessed on the Mini-Mental State Examination (MMSE), the Rowland Universal Dementia Assessment Scale (RUDAS) and an urban modification of the Kimberley Indigenous Cognitive Assessment (mKICA). Performance on these cognitive screening tools was compared to dementia diagnosis by clinical consensus. RESULTS: All tests were culturally acceptable with good psychometric properties. Receiver operating characteristic curve analyses revealed that the MMSE and mKICA were the most accurate. CONCLUSION: The MMSE is an effective cognitive screening tool in urban Aboriginal populations. The mKICA is a good alternative when illiteracy, language or cultural considerations deem it appropriate. The RUDAS also has adequate validity in this population.

Prevalence of dementia in urban and regional Aboriginal Australians.

BACKGROUND: This study aimed to determine the prevalence of dementia in collaboration with urban/regional Aboriginal communities. METHODS: A census of Aboriginal and Torres Strait Islander men and women aged 60 years and above in the target communities identified 546 potential participants, with 336 (61.5%) participating in this cross-sectional study. Participants completed a structured interview and cognitive screening tests. One hundred fifty-three participants also completed a detailed medical assessment. Assessment data were reviewed by a panel of clinicians who determined a diagnosis of dementia or mild cognitive impairment (MCI) according to standard criteria. RESULTS: Crude prevalence of dementia was 13.4%, and age-standardized prevalence was 21.0%. The most common types of dementia were Alzheimer's dementia (44%) and mixed dementia diagnoses (29%). Estimated prevalence of MCI was 17.7%. CONCLUSION: Consistent with previous findings in a remote population, urban and regional Aboriginal Australians face high rates of dementia at younger ages, most commonly Alzheimer's dementia.

Renin-angiotensin system genetic polymorphisms and brain white matter lesions in older Australians.

BACKGROUND: White matter lesions (WMLs), seen as hyperintensities on T2-weighted magnetic resonance imaging brain scans, are common in the brains of healthy older individuals. They are thought to be related to cerebral small vessel disease and to have a genetic component to their aetiology, and hypertension is thought to be an important risk factor. Genetic polymorphisms in hypertension-related genes may therefore be associated with the formation of WMLs. METHODS: In this study, a sample of 445 Australians aged 60-65 years was drawn from a larger longitudinal epidemiological study, the Personality and Total Health Through Life Project. The associations of single nucleotide polymorphisms (SNPs) in the genes encoding angiotensinogen (AGT, rs699), angiotensin-converting enzyme (ACE, rs4362), and angiotensin II receptor type 1 (AGTR1, rs5182) with WMLs were examined. RESULTS: No individual SNPs showed a significant association with WMLs for the whole sample. When the cohort was stratified by sex, ACE rs4362 and AGT rs699 showed significant associations with WMLs in men only (P = 0.01 and P = 0.03, respectively), and remained significant after controlling for hypertension. Although the AGTR1 SNP did not show any association with WMLs, the interaction of the AGT rs699 and AGTR1 rs5182 SNPs with WMLs was significant before (P = 0.03) and after adjustment for hypertension (P = 0.045). CONCLUSIONS: The results provide evidence for association of polymorphisms in the renin-angiotensin system genes with WMLs, independent of hypertension. Male-only associations with WMLs were found for the AGT rs699 and ACE rs362 polymorphisms. Moreover, for the entire sample an interaction between AGT and AGTR1 rs5182 genotypes on WMLs was observed.

The Koori Growing Old Well Study: investigating aging and dementia in urban Aboriginal Australians.

BACKGROUND: Dementia is an emerging health priority in Australian Aboriginal communities, but substantial gaps remain in our understanding of this issue, particularly for the large urban section of the population. In remote Aboriginal communities, high prevalence rates of dementia at relatively young ages have been reported. The current study is investigating aging, cognitive decline, and dementia in older urban/regional Aboriginal Australians. METHODS: We partnered with five Aboriginal communities across the eastern Australian state of New South Wales, to undertake a census of all Aboriginal men and women aged 60 years and over residing in these communities. This was followed by a survey of the health, well-being, and life history of all consenting participants. Participants were also screened using three cognitive instruments. Those scoring below designated cut-offs, and a 20% random sample of those scoring above (i.e. "normal" range), completed a contact person interview (with a nominated family member) and medical assessment (blind to initial screening results), which formed the basis of "gold standard" clinical consensus determinations of cognitive impairment and dementia. CONCLUSION: This paper details our protocol for a population-based study in collaboration with local Aboriginal community organizations. The study will provide the first available prevalence rates for dementia and cognitive impairment in a representative sample of urban Aboriginal people, across city and rural communities, where the majority of Aboriginal Australians live. It will also contribute to improved assessment of dementia and cognitive impairment and to the understanding of social determinants of successful aging, of international significance.

Stability of genetic influences on pulmonary function in a longitudinal study of octogenarian twins.

Using data from the first four waves of the OCTO-Twin study (twins 80 + years), the present study investigated the stability and change of genetic and environmental contributions to pulmonary function. Using a genetic simplex model, variance in peak expiratory flow (PEF) at each wave was decomposed into additive genetic and nonshared (specific) environmental factors. Additionally, this analysis distinguished the source of these influences, either from previous waves (transmissions) or from novel influences at each wave (innovations). At each time point (except wave 1), the genetic variance was due to genetic transmissions from prior time points. Conversely, the specific environmental variance in PEF at each time point was mainly due to environmental innovations. These results imply that genetic factors contribute to the stability of pulmonary function over time whereas environmental factors contribute to its change.

Alcohol consumption as a risk factor for dementia and cognitive decline: meta-analysis of prospective studies.

The relationships between alcohol consumption and dementia and cognitive decline were investigated in a systematic review including meta-analyses of 15 prospective studies. Follow-ups ranged from 2 to 8 years. Meta-analyses were conducted on samples including 14,646 participants evaluated for Alzheimer disease (AD), 10,225 participants evaluated for vascular dementia (VaD), and 11,875 followed for any type of dementia (Any dementia). The pooled relative risks (RRs) of AD, VaD, and Any dementia for light to moderate drinkers compared with nondrinkers were 0.72 (95% CI = 0.61-0.86), 0.75 (95% CI = 0.57-0.98), and 0.74 (95% CI = 0.61-0.91), respectively. When the more generally classified "drinkers," were compared with "nondrinkers," they had a reduced risk of AD (RR = 0.66, 95% CI = 0.47-0.94) and Any dementia (RR = 0.53, 95% CI = 0.53-0.82) but not cognitive decline. There were not enough data to examine VaD risk among "drinkers." Those classified as heavy drinkers did not have an increased risk of Any dementia compared with nondrinkers, but this may reflect sampling bias. Our results suggest that alcohol drinkers in late life have reduced risk of dementia. It is unclear whether this reflects selection effects in cohort studies commencing in late life, a protective effect of alcohol consumption throughout adulthood, or a specific benefit of alcohol in late life.

Bone, muscle, and physical activity: structural equation modeling of relationships and genetic influence with age.

Correlations among bone strength, muscle mass, and physical activity suggest that these traits may be modulated by each other and/or by common genetic and/or environmental mechanisms. This study used structural equation modeling (SEM) to explore the extent to which select genetic loci manifest their pleiotropic effects through functional adaptations commonly referred to as Wolff's law. Quantitative trait locus (QTL) analysis was used to identify regions of chromosomes that simultaneously influenced skeletal mechanics, muscle mass, and/or activity-related behaviors in young and aged B6xD2 second-generation (F(2)) mice of both sexes. SEM was used to further study relationships among select QTLs, bone mechanics, muscle mass, and measures of activity. The SEM approach provided the means to numerically decouple the musculoskeletal effects of mechanical loading from the effects of other physiological processes involved in locomotion and physical activity. It was found that muscle mass was a better predictor of bone mechanics in young females, whereas mechanical loading was a better predictor of bone mechanics in older females. An activity-induced loading factor positively predicted the mechanical behavior of hindlimb bones in older males; contrarily, load-free locomotion (i.e., the remaining effects after removing the effects of loading) negatively predicted bone performance. QTLs on chromosomes 4, 7, and 9 seem to exert some of their influence on bone through actions consistent with Wolff's Law. Further exploration of these and other mechanisms through which genes function will aid in development of individualized interventions able to exploit the numerous complex pathways contributing to skeletal health.

Blood pressure and heart rate QTL in mice of the B6/D2 lineage: sex differences and environmental influences.

A quantitative trait locus (QTL) approach was used to define the genetic architecture underlying variation in systolic blood pressure (SBP) and heart rate (HR), measured indirectly on seven occasions by the tail cuff procedure. The tests were conducted in 395 F(2) adult mice (197 males, 198 females) derived from a cross of the C57BL/6J (B6) and DBA/2J (D2) strains and in 22 BXD recombinant-inbred (RI) strains. Interval mapping of F(2) data for the first 5 days of measurement nominated one statistically significant and one suggestive QTL for SBP on chromosomes (Chr) 4 and 14, respectively, and two statistically significant QTL for HR on Chr 1 (which was specific to female mice) and Chr 5. New suggestive QTL emerged for SBP on Chr 3 (female-specific) and 8 and for HR on Chr 11 for measurements recorded several weeks after mice had undergone stressful blood sampling procedures. The two statistically significant HR QTL were confirmed by analyses of BXD RI strain means. Male and female F(2) mice did not differ in SBP or HR but RI strain analyses showed pronounced strain-by-sex interactions and a negative genetic correlation between the two measures in both sexes. Evidence for a role for mitochondrial DNA was found for both HR and SBP. QTL for HR and SBP may differ in males and females and may be sensitive to different environmental contexts.

The association of APOE genotype and cognitive decline in interaction with risk factors in a 65-69 year old community sample.

BACKGROUND: While the evidence of an association between the apolipoprotein E (APOE) *E4 allele and Alzheimer's disease is very strong, the effect of the *E4 allele on cognitive decline in the general population is more equivocal. A cross-sectional study on the lifespan effects of the *E4 allele 1 failed to find any effect of the *E4 allele on cognitive performance at ages 20-24, 40-44 or 60-64 years. METHODS: In this four year follow-up study, we reexamine the effect of *E4 in the sample of 2,021 individuals, now aged 65-69 years. RESULTS: Performance on the Mini-Mental State Examination (MMSE) was significantly poorer for *E4 homozygotes than heterozygotes or non-carriers. The effects of the *E4 genotype on cognitive decline over four years were found on the MMSE and Symbol-Digit Modalities test but only when controlling for risk factors such as head injury and education. Analyses were repeated with the exclusion of participants diagnosed with a mild cognitive disorder, with little change. CONCLUSION: It is possible that *E4 carriers become vulnerable to greater cognitive decline in the presence of other risk factors at 65-69 years of age.

Total and regional gray matter volume is not related to APOE*E4 status in a community sample of middle-aged individuals.

BACKGROUND: The APOE*E4 allele has been associated with greater gray matter atrophy and with Alzheimer's disease. The aim of this study was to investigate whether the relationship between cerebral gray matter atrophy and APOE*E4 genotype was also present in a community-dwelling, nondemented 60- to 64-year-old cohort. METHODS: Hippocampal and amygdalar volumes were manually traced and analyzed on 331 cranial T1-weighted magnetic resonance imaging (MRI) scans to detect differences associated with APOE*E4 genotype. Voxel-based morphometric (VBM) analyses were applied to detect regional gray matter volume differences. RESULTS: No total, hippocampal, or amygdalar gray matter volume difference was detected between APOE*E4 carriers and noncarriers. CONCLUSIONS: In nondemented 60- to 64-year-olds, there was no association between APOE genotype and gray matter volume using both region-of-interest analysis and VBM.

Corpus callosum size, reaction time speed and variability in mild cognitive disorders and in a normative sample.

Intra-individual variability in reaction time increases with age and with neurological disorders, but the neural correlates of this increased variability remain uncertain. We hypothesized that both faster mean reaction time (RT) and less intra-individual RT variability would be associated with larger corpus callosum (CC) size in older adults, and that these associations would be stronger in adults with mild cognitive disorders. A normative sample (n=432) and a sample with mild cognitive disorders (n=57) were compared on CC area, RT mean and RT variability adjusting for age, sex, education, APOE genotype, smoking, alcohol consumption, grip strength, visual acuity, handedness and lung function. Samples did not differ in CC area or intra-cranial volume. In the normative sample, simple RT (SRT) and choice RT (CRT) were negatively associated with CC area but there were minimal associations between CC area and intra-individual RT variability. In the mild cognitive disorders sample, SRT, CRT and intra-individual variability on the SRT task were associated with CC area. Increased RT variability explained up to 12.7 percent of the variance in CC area in the sample with mild cognitive disorders, but less than 1 percent of the variance in CC area in the normative sample. There were no associations with APOE genotype. We conclude that intra-individual variability is associated with CC area in mild cognitive disorders, but not in normal aging. We propose that biological limits on reserve capacity must occur in mild cognitive disorders that result in stronger brain-behavior relationships being observed.

Serum alkaline phosphatase activity is regulated by a chromosomal region containing the alkaline phosphatase 2 gene (Akp2) in C57BL/6J and DBA/2J mice.

Quantitative trait locus (QTL) analyses were conducted to identify chromosomal regions that contribute to variability in serum alkaline phosphatase (AP) enzyme activity in mice derived from the C57BL/6J (B6) and DBA/2J (D2) inbred strains. Serum AP was measured in 400 B6D2 F2 mice at 5 mo and 400 B6D2 F2 mice at 15 mo of age that were genotyped at 96 microsatellite markers, and in 19 BXD recombinant inbred (RI) strains at 5 mo of age. A QTL on the distal end of chromosome 4 was present in all sex- and age-specific analyses with a peak logarithm of odds (LOD) score of 20.36 at 58.51 cM. The Akp2 gene, which encodes the major serum AP isozyme, falls within this QTL region at 70.2 cM where the LOD score reached 13.2 (LOD significance level set at 4.3). Serum AP activity was directly related to the number of D2 alleles of a single nucleotide polymorphism in the 5'-flanking region of the Akp2 gene, although no strain-related differences in hepatic expression of Akp2 RNA were found. A variety of sequence polymorphisms in this chromosomal region could be responsible for the differences in serum AP activity; the Akp2 gene, however, with several known amino acid substitutions between protein sequences of the B6 and D2 strains, is a leading candidate.

Adjusting data to body size: a comparison of methods as applied to quantitative trait loci analysis of musculoskeletal phenotypes.

UNLABELLED: The aim of this study was to compare three methods of adjusting skeletal data for body size and examine their use in QTL analyses. It was found that dividing skeletal phenotypes by body mass index induced erroneous QTL results. The preferred method of body size adjustment was multiple regression. INTRODUCTION: Many skeletal studies have reported strong correlations between phenotypes for muscle, bone, and body size, and these correlations add to the difficulty in identifying genetic influence on skeletal traits that are not mediated through overall body size. Quantitative trait loci (QTL) identified for skeletal phenotypes often map to the same chromosome regions as QTLs for body size. The actions of a QTL identified as influencing BMD could therefore be mediated through the generalized actions of growth on body size or muscle mass. MATERIALS AND METHODS: Three methods of adjusting skeletal phenotypes to body size were performed on morphologic, structural, and compositional measurements of the femur and tibia in 200-day-old C57BL/6J x DBA/2 (BXD) second generation (F(2)) mice (n = 400). A common method of removing the size effect has been through the use of ratios. This technique and two alternative techniques using simple and multiple regression were performed on muscle and skeletal data before QTL analyses, and the differences in QTL results were examined. RESULTS AND CONCLUSIONS: The use of ratios to remove the size effect was shown to increase the size effect by inducing spurious correlations, thereby leading to inaccurate QTL results. Adjustments for body size using multiple regression eliminated these problems. Multiple regression should be used to remove the variance of co-factors related to skeletal phenotypes to allow for the study of genetic influence independent of correlated phenotypes. However, to better understand the genetic influence, adjusted and unadjusted skeletal QTL results should be compared. Additional insight can be gained by observing the difference in LOD score between the adjusted and nonadjusted phenotypes. Identifying QTLs that exert their effects on skeletal phenotypes through body size-related pathways as well as those having a more direct and independent influence on bone are equally important in deciphering the complex physiologic pathways responsible for the maintenance of bone health.