Bone – The Hardest Frontier

The adult human body contains 206 separate bones of various shapes and sizes.

Our bones have many functions. They provide support for our bodies and protection to our softer internal organs and enable us to walk and move around. Bones are continuously turned over and regenerate throughout our lives, though this diminishes as our bodies’ age.

The hard outer layer of bone provides support for our body and the muscles and ligaments attached to it allow for simple and complex movements. However, bone is so much more than just a hard skeleton. Like other parts of the body, bones are made up of active cells that grow and repair. Bones also store and release certain minerals that are critical for healthy body functioning such as calcium, magnesium and phosphate. The soft interior of our large bones, the bone marrow, carries out a number of vital functions, important among which is the manufacture of white and red blood cells and platelets.

The two most active bone cells are: osteoblasts, whose role is to build bone and osteoclasts whose function is to breakdown and reabsorb bone, so as to prevent overgrowth and maintain shape and structure. These two cells work together to maintain a healthy bone structure, building bone when necessary, such as during growth or fracture repair. Bone growth reacts to bodily demands. It may increase and thicken where more demands are made of it, such as in athletes, or, it may thin when less demands are made upon it, such as in older age where body weight and movement decline.

Bones have their own vasculature, contained within pores throughout the bone, thus blood is able to reach the bone, allowing interchange of substances such as oxygen and minerals into the bone and waste products and required minerals out of the bone. However, blood supply to the dense bone shell is significantly less than that to other softer organs of the body and its naturally hard surface makes uptake of drugs more difficult to achieve.

Clinical conditions of bone may relate to either the hard structure, or be within the softer inner core, the bone marrow.

Conditions related to the hard structure can include:

  • Excessive loss of essential minerals, such as calcium, which results in the bone structure becoming weaker and potentially fractures occurring (osteoporosis).
  • Excessive and uncontrolled bone growth such as in bone cancer (osteosarcoma) or, certain bones growing abnormally (e.g. Pagett’s Disease) or, bone growing in other organs, such as muscle (e.g. fibrodysplasia ossificans or heterotopic ossification associated with trauma or disease).
  • Fractures that don’t heal quickly or adequately (non-union fractures).
  • Joint bones that become damaged due to either “wear and tear” (osteo-arthritis) or, are damaged due to a fault in the immune system causing the body to attack itself (rheumatoid arthritis).
  • Insufficient bone or reduced bone growth where necessary to support teeth repair or prosthetic implants.

Conditions related to the bone marrow can include:

  • Infections by bacteria localizing inside bone (osteomyelitis).
  • Cancer, such as of bone itself (osteosarcoma) or within bone such as excess white blood cell production (leukemia) or, growth of cancer cells within the bone from other tumors (metastases).
  • Overgrowth of cells within the bone marrow and aberrant blood cell production as seen in myelofibrosis.
  • Deformed red blood cell production (thalassemia and other anemias) resulting in an expansion of bone marrow and subsequent bone fractures.
  • Debilitating bone pain, often associated with cancer.

Current treatments are hampered by the difficulty of getting the necessary therapeutic onto or into bone at sufficiently high enough concentration to be effective without generating unacceptable side effects, or, having to treat for extended periods of time.