The goal of this clinical trial is to investigate whether different types of small meals can help reduce bone loss in postmenopausal women with osteopenia, a condition where bone density is lower than normal and may lead to osteoporosis.

The main hypothesis is:

- A small amount of dairy (100 ml) is just as effective as a larger meal containing dairy and banana in reducing bone resorption.

Based on this, the study aims to answer the following questions:

- Which type and size of meal is most effective in reducing bone resorption?

Researchers will compare five different types of meals to a fasting control day to determine which meals best reduce markers of bone loss in the blood.

Participants will attend six clinical visits: five involving the intake of different test meals, and one control visit involving fasting. The participants will have blood samples taken over a period of 6 hours after each meal or fasting period to measure markers of bone metabolism.

This study aims to identify a simple, non-drug-based strategy to support bone health and help prevent progression to osteoporosis.

This project investigates whether administration of a meal can reduce bone resorption and thereby, if used strategic, prevent the development of osteoporosis in postmenopausal women with osteopenia, as measured by bone turnover markers and bone density. Furthermore, it is investigated which type and size of meal is optimal for bone health in osteopenia.

The project comprises of one hypotheses:

- 100 ml dairy is as effective as larger amounts of dairy and banana in decreasing bone resorption.

Osteopenia is a prevalent condition and is a precursor to osteoporosis and fractures. In 2011 it is estimated that osteoporotic fractures resulted a total cost of 1.6 billion EUR in Denmark. Osteopenia is diagnosed by a low bone mineral density (BMD), with a T-score between -1.1 and - 2.4, whereas osteoporosis is diagnosed by a T-score of ≤2.5. In postmenopausal women, it is estimated that 43 % have osteopenia. The current recommendation to prevent fractures in osteopenia is sufficient intake of vitamin D and calcium, besides smoking cessation, physical activity, and moderate alcohol intake. In case of osteoporosis, additional anti-osteoporotic medications are recommended, which have been shown to reduce fracture rates. However, effective non-pharmacologic remedies to prevent progression from osteopenia to osteoporosis are urgently needed and the potential of timing of meals in this context should therefore be explored. Osteopenia and osteoporosis are caused by an increased bone resorption to bone formation ratio which decreases BMD and increases fractures. During the bone resorption and bone formation phases; products are released to the bloodstream and can be measured as bone turnover markers. Carboxy-terminal collagen crosslinks (CTX) is a bone resorption marker and procollagen type I Npropeptide (P1NP) is a bone formation marker and they are internationally recommended as the standard bone turnover markers. Following a meal, bone resorption decreases. The gut hormone; glucagon-like peptide 2 (GLP-2) is released to the circulation following a meal and reduces bone resorption, as measured by CTX, by 50 %. In humans bone resorption is highly increased during the night time (fasting state) and gut hormones have therefore been suggested as treatments for osteoporosis. In a previous study, GLP-2 was administered subcutaneously before bedtime for 120 days and showed a decrease in nightly CTX levels and an increase in bone mineral density at the hip and no signs of tachyphylaxis during the treatment. The investigators have shown that a meal suppresses CTX levels for as long as six hours with a simultaneous increase in GLP-2 and that the oral administration of nutrients is essential for a reduction in CTX. The investigators have great experience in conducting clinical trials assessing bone health. In this project it is investigated which type and size of meals reduce CTX most profoundly.

The meals in this study are selected as 3.5 % fatty dairy or banana as these are commonly used smaller meals. Furthermore, the gastric emptying of a dairy depends on the meal size, and fat reduces the gastric emptying, whereas banana contains fibers and may thus have a shorter gastric emptying. Yoghurt is expected to have slower gastric emptying than milk primarily due to its higher viscosity. Additionally yoghurt is a more fermented product compared to milk, potentially affecting the postprandial gut hormone response differently. Psyllium and banana (pectin fibers) are both dietary fiber sources but differ in fiber composition and solubility, which may lead to different effects on gastric emptying and gut hormone responses. The fiber content differs between banana and psyllium, with psyllium being more concentrated. We aim to adjust the fiber content to be approximately equivalent, so participants will receive 4-5 g of psyllium (1 teaspoon), providing about the same amount of fiber as 100 g of banana.

The results from this study will be used for a follow up study in which the effects on bone health of meal administration over a longer period will be assessed.

Inclusion Criteria:

• Osteopenia at the lumbar spine defined as BMD t-score -2.4 to -1.1.
• Postmenopausal women
• Age < 80 years
• CTX level ≥ 0.40 ng/ml
• BMI 17-25 kg/m2

Exclusion Criteria:

• A diagnosis of osteoporosis, diabetes, primary hyperparathyroidism or active malignancy.
• Current or recent (within two years) use of systemic glucocorticoids for 4 continuous weeks or more, anticonvulsants or anti-osteoporotic drugs including systemic estrogen treatment.
• Low p-25-OH vitamin D-levels (< 50 pmol/l)
• Estimated glomerular filtration (eGFR) <60 ml/min

Blinding of participants is not possible, laboratory staff who will analyse the blood samples, will be blinded to the intervention.