Background:​

Osteoporosis commonly affects older men and women. Frequently, it is caused or exacerbated by a disease or treatment (termed secondary osteoporosis). The aim of this thesis is to explore aspects of the pathogenesis and treatment of three conditions that may cause or contribute to osteoporosis:​ human immunodeficiency virus (HIV) infection, primary hyperparathyroidism (PHPT), and vitamin D insufficiency. Each of these conditions is potentially linked to bone metabolism via associations with nutritional status, which in turn is a key regulator of bone mass and fracture risk.

Methods:​

Eight studies were performed:​

1. Cross-sectional comparison of bone mineral density (BMD) in HIV-infected men and age- matched controls.
2. Two-year randomised controlled trial of the effects of annual zoledronate on BMD in HIV- infected men.
3. Longitudinal comparison of the change in BMD over two years in HIV-infected men not receiving skeletal therapy and controls.
4. Meta-analysis of body weight in patients with PHPT.
5. Cross-sectional analysis of the relationship between parathyroid hormone and body weight in post-menopausal women.
6. Cross-sectional analysis of the determinants of 25-hydroxyvitamin D (25OHD) in post- menopausal women and middle-aged and older men.
7. Cross-sectional analysis of the effects of fat mass and seasonal variation on diagnosis of vitamin D sufficiency.
8. Cross-sectional analysis of the relationship between vitamin D binding protein and body weight in older men and women.

Results:​

1. HIV-infected men were 6.3 kg lighter than controls, and after adjustment for this weight difference, did not have lower BMD than controls.
2. Annual intravenous zoledronate caused substantial increases in BMD in HIV-infected men over two years.
3. HIV-infected men did not have accelerated bone loss over time compared to controls.
4. Patients with PHPT are on average 3.1-3.3 kg heavier than age-matched controls.
5. Fat mass is an important determinant of parathyroid hormone levels.
6. The major determinants of 25OHD levels in men and women are surrogate measures of ultraviolet-B exposure, and fat mass, but men have higher 25OHD levels throughout the year than women.
7. Thresholds for diagnosis of vitamin D sufficiency vary by season and amount of fat mass.
8. Vitamin D binding protein does not mediate the relationships between 25OHD and age, gender or weight.

Conclusions:​

Uncomplicated HIV infection is not associated with low BMD at baseline or accelerated bone loss over time. There are important relationships between body weight and PHPT, and among fat mass, parathyroid hormone and 25OHD that have significance both for the pathogenesis of PHPT and vitamin D sufficiency, and for the clinical diagnosis and treatment of these conditions.