Utility of Cortical Bone Tissue Properties in the Assessment of Fracture Risk

The objective of this study is to determine whether a new minimally invasive method for in
vivo measurement of cortical bone tissue properties can identify those who are at risk for
fragility fractures of the hip and radius. The investigators hypothesis is that women with
fragility fractures of the hip and radius have altered cortical bone tissue properties
compared to non-fracture controls independent of standard clinical tests, such as BMD. To
test these hypotheses, The investigators propose two aims:

Aim 1: Compare cortical bone tissue properties as assessed in vivo by reference point
indentation in women with hip fractures and non-fracture controls.

The investigators will compare cortical bone tissue material properties, as assessed by novel
in vivo indentation at the mid-tibia in postmenopausal women with recent hip fractures (n)
and age-similar controls without fractures (n=). In addition to in vivo indentation
measurements, The investigators will assess hip and spine BMD by DXA; as well as other
factors that may influence risk of fractures (e.g, vit D status, medication use and physical
activity). Hypotheses: Postmenopausal women with hip fractures will have worse bone tissue
material properties compared to non-fracture controls even after adjustment for BMD and other
potential confounders.

Aim 2: Compare cortical bone tissue properties as assessed in vivo by reference point
indentation in women with distal radius fractures to non-fracture controls.

The investigators will compare cortical bone tissue material properties, as assessed by novel
in vivo indentation at the mid-tibia in postmenopausal women with recent distal radius
fractures (n) and age-similar controls without fractures (n=). In addition to in vivo
indentation measurements, The investigators will assess hip and spine BMD by DXA; as well as
other factors that may influence risk of fractures (e.g, vit D status, medication use and
physical activity). Hypotheses: Postmenopausal women with distal radius fractures will have
worse bone tissue material properties compared to non-fracture controls even after adjustment
for BMD and other potential confounders.

Successful completion of this project will address the need to better assess bone mechanical
properties at the tissue level in order to accurately predict fracture risk. The study will
provide novel information about possible clinical utility of minimally invasive, in vivo bone
indentation measurements to measure bone strength and its relationship to fracture risk.

Aim 3: An amendment to the protocol expanded the study population to now include males >50
years who present with distal radius fractures and those who present for a reason other than
fracture (non-fracture controls). Hypotheses: Men >50 years with distal radius fractures will
have worse bone tissue material properties compared to non-fracture controls even after
adjustment for BMD and other potential confounders.

Inclusion Criteria:

- Women with hip and wrist fractures within 2 weeks of presentation

- Non-fracture controls

Exclusion Criteria:

- Unable to undergo BMD by DXA or high-resolution peripheral quantitative computed
tomography (HR-pQCT)

- History of skeletal metastasis, primary hyperparathyroidism, Paget's disease, multiple
myeloma

- Treatment with bisphosphonate, estrogen (within previous 3 years), teriparatide
therapy, calcitonin, selective estrogen receptor modulator (SERMs,within previous 3
years)

- Use of glucocorticoids continuously for more than 3 months, use of anticonvulsants

- Prior fracture in adulthood (>age 18) for healthy controls

Amendment to protocol added Arm 2, to include males >50 years with otherwise similar
eligibility criteria.