Bone mineral (hydroxyapatite)

aka Hydroxyapatite, bone mineral matrix

The hard mineral that makes up bone. Certain radioactive drugs stick to this mineral wherever bone is being actively rebuilt, which is how bone scans find fractures, infection and cancer that has spread to bone, and how some treatments deliver radiation straight to bone metastases.

Bone is a composite of collagen protein and hydroxyapatite, a crystalline calcium phosphate mineral (Ca5(PO4)3OH). Bisphosphonates - and the older diphosphonates such as methylene diphosphonate (MDP) and hydroxymethylene diphosphonate (HDP/HMDP) - bind hydroxyapatite with high affinity through a P-C-P backbone that chelates surface calcium ions in a bidentate arrangement; when labelled with technetium-99m, the resulting Tc-99m-MDP or Tc-99m-HDP complex accumulates on bone in proportion to local blood flow and osteoblastic activity (new bone formation provides more, smaller hydroxyapatite crystals with greater surface area for binding), which is the basis of conventional bone scintigraphy.

A related but chemically distinct mechanism is direct ionic exchange: 18F-fluoride ions substitute for hydroxyl groups in the hydroxyapatite lattice to form fluoroapatite, giving even faster, higher-contrast bone-turnover imaging on PET than Tc-99m bone scans. On the therapy side, the same hydroxyapatite affinity is exploited by bone-seeking radionuclide therapies: samarium-153 lexidronam (a Sm-153-EDTMP bisphosphonate complex) and radium-223 dichloride (a calcium mimetic incorporated directly into the mineral at sites of osteoblastic activity) both concentrate in areas of high bone turnover, including osteoblastic bone metastases, to deliver localised radiation for pain palliation or, for radium-223, a survival benefit in castration-resistant prostate cancer with bone metastases.

As a target, hydroxyapatite's strength is that bone-turnover tracers and therapies go wherever remodelling is happening, with no receptor saturation or internalisation step required (bone-seeking agents work by chemisorption or ionic exchange, not receptor binding). Its central weakness is a lack of disease specificity: fractures, arthritis, Paget's disease and infection all increase osteoblastic activity and light up alongside malignancy, so bone scans are sensitive but not specific, and specificity depends entirely on the clinical and radiological context.

Bone mineral (hydroxyapatite): what it is and how drugs act on it · animated schematic, not to scale

Target · the protein and the cell it sits on
Drug · antibody, small molecule, cell or radioligand
Effect · signal, damage or kill

In plain words · The hard mineral that makes up bone. Certain radioactive drugs stick to this mineral wherever bone is being actively rebuilt, which is how bone scans find fractures, infection and cancer that has spread to bone, and how some treatments deliver radiation straight to bone metastases.

1 · What it is
The hard mineral that makes up bone. Certain radioactive drugs stick to this mineral wherever bone is being actively rebuilt, which is how bone scans find fractures, infection and cancer that has spread to bone, and how some treatments deliver radiation straight to bone metastases.
2 · What goes wrong in cancer
The crystalline calcium phosphate mineral phase of bone, bound to a collagen matrix.
3 · How drugs use it
No product in this corpus aims at Bone mineral (hydroxyapatite) yet. Drugs bind the molecule precisely: to switch it off, flag the cell for the immune system, or deliver a payload.

External identifiers

Biology

The crystalline calcium phosphate mineral phase of bone, bound to a collagen matrix. Bisphosphonates and fluoride ions bind or exchange with this mineral at sites of active bone turnover through chemisorption or ionic substitution respectively, concentrating radiotracers or radionuclide therapy wherever bone remodelling, including reactive new bone at metastases, is occurring.

Where it is found

Sites of active bone remodelling generally: fractures, degenerative and inflammatory bone disease, Paget's disease, infection
Osteoblastic bone metastases (prostate, breast and other cancers): increased uptake reflecting reactive new bone formation
Normal growing skeleton: high uptake at epiphyseal growth plates and osteochondral junctions

Class

other