Participants
Participants were from the Geelong Osteoporosis Study (GOS), a population-based cohort study situated in a geographically well-defined region in south-eastern Australia, known as the Barwon Statistical Division. Details of recruitment and retention have been described elsewhere [21]. The male arm of the GOS commenced in 2001 with recruitment of 1540 men aged 20-92 years. Participants are re-assessed every few years and data for this cross-sectional analysis were generated for 390 men assessed in 15-yr follow-up phase (ages 40 to 90 years). The study was approved by the Human Research Ethics Committee at Barwon Health. All participants provided written informed consent. We confirm that the conduct of the study adhered to the STROBE statement for cohort studies and Good Clinical Practice. All methods were performed in accordance with the relevant guidelines and regulations.
Impact microindentation (IMI)
Using the OsteoProbe RUO (Active Life Technologies, Santa Barbara, CA, USA), BMSi was measured on the anterior surface of the mid-tibia following standard guidelines [22]. The indentation site was determined by measuring the midpoint from the medial border of the tibial plateau to the distal edge of the medial malleolus. Following disinfection of the area
administration of local anesthetic, the OsteoProbe was inserted through the skin and periosteum until reaching the surface of the bone at the anterior face of the mid-tibia. At least 11 indentations were performed for each participant, of which the first measurement was systematically disregarded followed by 10 valid test indentations. The first measurement was disregarded to ensure sufficient penetration of the probe through the periosteum. Two trained operators conducted the IMI measurements (PR-M and KLH-K). The coefficient of variation (CV) for microindentation was 2% for repeated measures. Precision was calculated as the mean (expressed as %) of SD/mean for 2 sets of indentations for 10 participants.
Bone mineral density
Areal BMD (g/cm2) was measured at the femoral neck using DXA (Lunar, Prodigy, Madison, WI, USA). Quality control was maintained through weekly measurements of a Lunar DXA phantom. Height and weight were measured to the nearest 0.1cm and 0.1kg, respectively.
Medical history, lifestyle factors and FRAX score
All participants completed comprehensive questionnaires detailing medical history, medication use and lifestyle behaviours. The FRAX probability for a major osteoporotic fracture (MOF) and for a hip fracture (HF) was calculated using the Australian FRAX tool [16]. For each participant, four 10-year probability scores were generated: (i) MOF-FRAXnoBMD; (ii) MOF- FRAXBMD;
(iii) HF-FRAXnoBMD (iv) HF-FRAXBMD.
FRAX scores are based on risk factors for fracture including age, sex, weight, height, previous fracture, parental history of hip fracture, glucocorticoid use, rheumatoid arthritis, secondary osteoporosis, current smoking and alcohol use. Both fracture probabilities were computed with and without the inclusion of femoral neck BMD. A prior fracture was defined as any low trauma fracture equivalent to a fall from a standing height or less, excluding fractures of the toe, skull, finger and face, occurring during adulthood (age ≥20 years). Prior fractures were radiologically verified where possible. A parental hip fracture referred to at least one maternal or paternal hip
fracture. Current smoking referred to use of tobacco at least daily and excessive alcohol
consumption as ≥3 units daily on average. Oral glucocorticoid use and rheumatoid arthritis were self-reported. Secondary osteoporosis including type 1 (insulin dependent) diabetes was determined, as previously described [23]. Osteogenesis imperfecta in adults, untreated long-standing hyperthyroidism and chronic liver disease were self-reported. A BMI <18.5kg/m2 (underweight) was used as a surrogate indicator of chronic malnutrition.
Statistical Analysis
BMSi values were visually assessed for normality. Based on the USA-adapted World Health Organization (WHO) treatment threshold (≥ 3% for HF and ≥ 20% for MOF) [24], FRAX scores were categorised into high and low. Associations between BMSi values and FRAX scores were identified using Pearson’s correlation. Statistical analyses were performed using Minitab V.18 (State College, Pennsylvania, USA).