Public defense: Annette Vogt Flatby

Osteoporosis is a widespread condition among older adults that increases the risk of fractures due to structural weakening of the skeleton.

The condition is defined by an areal bone mineral density (aBMD) level lower than 2.5 standard deviations (SD) below the mean of a young, healthy reference population. Osteopenia is the precursor to osteoporosis and is defined by an aBMD of –1 to –2.5 SDs compared to the mean of the reference population.

aBMD increases through the first two to three decades of life before it reaches its peak and then starts to decrease around the age of fifty. Women experience a larger and earlier aBMD decrease than men due to cessation of estrogen production during menopause and are therefore more likely to develop osteoporosis than men.

In addition, there are great variations in the magnitude of the peak bone mass and the subsequent rate of bone loss between individuals. Muscle tissue influences the formation of bone tissue and vice versa. It is therefore reasonable to assume that muscle performance is positively associated with aBMD, but the association between standardized physical capability tests and aBMD has not been extensively examined.

We know that osteoporosis gives an increased risk of fractures and there seems to be an association between low aBMD and higher mortality but does low aBMD in the form of osteopenia or osteoporosis also predict mortality independent of fractures?

Also, if low aBMD is associated with higher mortality, is mortality higher for those who experience a high rate of bone loss over a period? And do people with higher levels of physical capability and physical activity have higher aBMD? These questions will be investigated in the thesis.

The PhD work was performed in the period 2017 to 2022 using data from the Tromsø study waves 4 (1994-95), 5 (2001-02) and 7 (2015-16), the Norwegian Cause of Death Registry and the National Population Registry. 

In our first study (article I), we used data from the fourth wave of the Tromsø study (Tromsø4) to assess mortality during 22 years of follow-up for participants who had normal aBMD, osteopenia or osteoporosis at baseline based on aBMD measurements of the distal forearm. We also tested the association between BMD and mortality for interaction by grip strength.

Using Cox-regression models adjusted for relevant lifestyle- and health-related variables, we found both osteopenia and osteoporosis to be associated with significantly higher mortality compared to normal aBMD in both women and men (women: HR 1.17 (CI 1.01 to 1.35) and 1.32 (CI 1.14 to 1.53), men: HR 1.13 (CI 1.00 to 1.27) and 1.37 (CI 1.19 to 1.58)).

Grip strength did not interact with the association. In additional analyses adjusted for fractures, we still found significantly higher mortality in both women and men with osteoporosis.

In our second study (article II), we investigated if bone loss in the distal forearm over seven years (between Tromsø4 and Tromsø5) was associated with mortality during 17 years follow-up in people with normal and low aBMD at baseline. Cox-regression models adjusted for relevant lifestyle- and health-related variables were used for the analyses.

Bone loss was categorized as 1: “increased or unchanged”, 2: “2 to 4% decrease” or 3: “more than 4% decrease”. In the models, bone loss was only associated with mortality in those with normal aBMD at baseline and only in men; category 3 bone loss was associated with 50% higher mortality than category 1 (HR 1.50, CI 1.21 to 1.87).

In our third study (article III), we used data from Tromsø7 to assess the associations between total hip aBMD and physical capability and self-reported leisure-time physical activity assessed by standard (/established/validated?) tests. The tests included were hand grip strength, the Timed Up and Go test (TUG), one-leg-balance and the Short Physical Performance Battery (SPPB) including time spent on the SPPB sub-tests chair-stand test and 4-meter walk as individual tests.

Linear regression analyses adjusted for health and lifestyle-related variables were performed for each test individually to test for association with aBMD and both standardized and unstandardized beta-coefficients were calculated. Better performance on any of the tests were associated with higher aBMD in women.

In men, only performance on the SPPB and its sub-tests “chair-stand test” and “4-meter walk” were associated with aBMD. In both women and men, vigorous physical activity four or more hours per week was associates with significantly higher aBMD compared to a sedentary lifestyle. In women, moderate and very hard physical activity was also associated with a higher aBMD.