Optimising Bone Health in Cancer

The structure of the bone

Your bone is made up of a dense protective outer layer of compact bone called the cortex, and an inner honeycomb-like network of spongy bone. It is made up of collagen for flexibility and calcium for hardness. Bones protect, support, and produce and store blood cells and minerals.

Bone cells play a crucial role in the health of the bone. Cells called osteocytes maintain the bone matrix, whilst osteoblast form new bone and osteoclast breakdown old bone for remodelling. The growth of your bone is regulated by several hormones and signalling pathways including estrogen and androgen in puberty.

G-Protein coupled receptor 133 (GPR133/ADGR1)

GPR133 is a major receptor, expressed on the osteoblast (cells responsible for forming new bone). It is essential for healthy bone formation and it increases the bone strength when it is signalled.

When this receptor is stimulated it:

o   Enhances osteoblast activity – bone forming cell

o   Suppresses osteoclast activity – the bone reabsorbing cell

o   Improves bone density and resilience

Why is GPR133 relevant?

Research has shown that GPR133 responds to mechanical strain and cell to cell signals and triggers a pathway that increases bone formation and reduces bone resorption.

That means it responds to mechanical strain to remodel bone appropriately and is shown to strengthen bones even in osteoporosis like conditions.

What can you do to activate GPR133?

GPR133 is a mechanosensitive receptor. That means it is activated or switched on when bones experience physical stress, movement and loading forces.  

Bone health and cancer

The sex hormones estrogen or testosterone is needed for bone strength. In some cancers such as breast and prostate cancer, the use of hormone deprivation therapy, needed for cancer treatment, can speed up bone loss and increase the risk of osteopenia, osteoporosis and fractures through rapid bone breakdown, causing measurable bone density loss within 12 months.

How can exercise help?

Loading exercises such as resistance exercises and impact type exercise training stimulates GPR133 receptors and so helps to maintain and improve bone health. Evidence shows that these types of exercises can help to improve bone loss and bone health in persons with cancer when exercises are carefully prescribed and individualised.  

A recent study reviewing the evidence on exercise in cancer with bone loss or metastases found that supervised resistance training with impact/weight-bearing or aerobic exercise:

Has a small but favourable effect on bone mineral density and bone turnover in those with bone loss or metastases.

Exercise generally maintained bone outcomes rather than improved them.

Exercise was safe when tailored to lesion location and bone stability.

Exercise was feasible with appropriate screening and modification.

Type of exercises for bone health in cancer

When thinking of starting any exercise during or following cancer treatment it is important to first consult your medical team who will be able to advice you or refer you to a specialist. Always seek advice from expert professionals. 

Start with gentle walking as this will provide some impact and mechanical loading. Resistance training of large muscle groups will also provide mechanical load which in turn will stimulate GPR133 receptors and assist in maintaining bone health.

Each individual has their own cancer diagnosis, treatment and health requirements; and so consideration is crucial when prescribing exercises. Exercises need to be individualised and care personalised.

In summary

Some cancer treatment can affect the health of your bones causing bone loss and an increased risk of osteopenia, osteoporosis and fractures. A recent early clinical research has identified a receptor called GPR133 which helps to keep the bone strong through daily activities which cause mechanical loading.

Another research study found that loading exercise was safe and feasible in persons diagnosed with cancer and it maintained bone outcomes.

Persons diagnosed with cancer require appropriate screening and exercise modification.

References

Borsati A, Adamoli G, Giannarelli D, Belluomini L, Trevisan A, Schenal P, Bettariga F, Markarian AM, Schena F, Milella M, Newton RU, Pilotto S, Avancini A. Effect of exercise on bone-related outcomes in patients with cancer affected by bone metastases or bone loss: a systematic review and meta-analysis. Osteoporos Int. 2025 Dec;36(12):2381-2399.

doi: 10.1007/s00198-025-07645-4. Epub 2025 Aug 6. PMID: 40764418; PMCID: PMC12672621.

Cowan PT, Launico MV, Kahai P. Anatomy, Bones. [Updated 2024 Apr 21]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2026 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK537199/

Lehmann J, Lin H, Zhang Z, Wiermann M, Ricken AM, Brinkmann F, Brendler J, Ullmann C, Bayer L, Berndt S, Penk A, Winkler N, Hirsch FW, Fuhs T, Käs J, Xiao P, Schöneberg T, Rauner M, Sun JP, Liebscher I. The mechanosensitive adhesion G protein-coupled receptor 133 (GPR133/ADGRD1) enhances bone formation. Signal Transduct Target Ther. 2025 Jun 30;10(1):199.

doi: 10.1038/s41392-025-02291-y. PMID: 40583059; PMCID: PMC12206920.