1.1 Bone Anatomy, Cellular Composition & Matrix
Key Takeaways
Secondary osteons have lamellae around a vascular canal. Trabecular bone is arranged as a network of plates and rods.
Osteoblasts deposit osteoid, osteocytes are embedded cells and osteoclasts resorb bone. Lining cells cover resting surfaces.
Osteoclast proton transport promotes mineral dissolution. Cathepsin K contributes to organic matrix degradation.
A DXA measurement reflects projected mineral. It cannot separately establish compartment porosity or the cause of a mineral deficit.
Read bone as a structure with two compartments
Bone supports and protects the body, houses marrow and stores mineral. Cortical bone forms the compact shell and is particularly prominent in the shafts of long bones. Much of mature cortical bone contains secondary osteons. Each consists of lamellae around a central Haversian canal. Perforating canals, commonly called Volkmann canals, connect vascular channels. A cement line delineates a secondary osteon from surrounding bone. Cortical tissue also contains interstitial and circumferential lamellae. The periosteum covers much of the outer bone surface, and endosteal surfaces line the internal bone spaces.
Trabecular bone forms a three-dimensional network of plates and rods separated by marrow spaces. It is prominent in vertebral bodies and toward the ends of long bones. The marrow-facing surfaces support remodeling. Both compartments contain osteocytes embedded in mineralized matrix. Their processes extend through canaliculi, linking lacunae to other cells and nearby surfaces. Human specimens show variation in osteon orientation, mineral organization and the arrangement of trabeculae. Exact fractions and dimensions depend on site, specimen and method.
| Location | What the measured region represents |
|---|---|
| PA lumbar spine | A projection through vertebral structures, including posterior elements. The trabecular-rich vertebral body is only part of the projected region. |
| Femoral neck and total hip | Regions containing both cortical and trabecular bone. Cortical thickness and compartment contributions vary across the proximal femur. |
| One-third radius | A cortical-rich region used for diagnosis when forearm DXA is indicated. The ultradistal region is a different region with a greater trabecular contribution. |
A clinician evaluating a patient with established primary hyperparathyroidism adds a forearm scan because hyperparathyroidism is an ISCD indication. The diagnostic region is the one-third radius of the non-dominant forearm. Its cortical predominance helps explain the clinical value of assessing it in this setting. Its T-score describes the regional measurement and cannot establish the biochemical diagnosis or isolate cortical porosity.
Connect the cell to its task
| Cell | Origin or location | Relevant function |
|---|---|---|
| Osteoblast | Mesenchymal stromal progenitors, differentiating at bone surfaces | Deposits osteoid and supports mineralization. Experimental work identifies RUNX2 and SP7 (osterix) as important differentiation regulators. |
| Bone lining cell | Flattened osteoblast-lineage cell on quiescent surfaces | Covers resting surfaces and can participate in the transition to active formation. |
| Osteocyte | Former osteoblast embedded in matrix | Senses the mechanical environment and participates in local and endocrine signaling. |
| Osteoclast | Hematopoietic monocyte/macrophage lineage | Multinucleated cell that resorbs mineralized bone. M-CSF and RANKL help support development and differentiation. |
A mature osteoclast adheres to bone and develops a sealing zone and ruffled border. A vacuolar proton pump acidifies the resorption compartment. Acid promotes mineral dissolution, and proteases, especially cathepsin K, degrade organic matrix. Experimental cathepsin K deficiency can impair matrix degradation while demineralization is preserved. An osteoblast can become an embedded osteocyte or a surface lining cell, or undergo cell death. The relative frequencies depend on the setting.
Osteocytes influence how bone responds to loading. In a controlled ulnar-loading animal experiment, loaded regions showed reduced expression of Sost and its protein sclerostin. Sclerostin inhibits Wnt signaling, which participates in osteoblast differentiation and function. The experimental finding illustrates an adaptation pathway. It does not quantify the response to a prescribed exercise in an individual.
Distinguish osteoid from mineralized tissue
Osteoblasts deposit osteoid, the unmineralized organic matrix, rich in type I collagen and containing other matrix proteins. Bone mineral is a calcium phosphate apatite with substitutions such as carbonate. Mineral, collagen and water interact at several structural scales. Mineral contributes stiffness. The collagen-rich matrix contributes to deformation and energy dissipation. A measurement of mineral content cannot independently describe these material properties.
Mineral deposition depends on local regulation. Tissue-nonspecific alkaline phosphatase reduces extracellular pyrophosphate, an inhibitor of mineral propagation. Deficiency can impair mineralization. Osteoid formation, mineralization and bone resorption describe different processes. For example, lower measured mineral can occur with reduced bone volume or with impaired mineralization of existing matrix, and DXA alone does not identify which process is responsible. Bone composition can also affect X-ray attenuation. Strontium incorporation can increase apparent DXA BMD, with effects dependent on the device and strontium content. A single universal numerical correction cannot be applied to an individual scan.
Human osteon imaging · Trabecular structure study · RUNX2 experiment · SP7 experiment · Osteoclast proton pump · Cathepsin K experiment · Loading experiment · TNAP experiment · Strontium attenuation · ISCD Adult Official Positions · Fifth PHPT Workshop
Which pair of processes supports mature osteoclast resorption of mineralized bone?
Acidification by vacuolar proton pumps and organic matrix degradation by cathepsin K.
Pyrophosphate hydrolysis by osteoblast alkaline phosphatase and secretion of new osteoid.
Sclerostin binding to RANK and promotion of mineral precipitation.
Cortical canaliculi secreting collagen to isolate the ruffled border.
A clinician adds forearm DXA for a patient with established primary hyperparathyroidism. Which region is used for diagnosis under the ISCD adult positions?
The ultradistal radius because it has a larger trabecular contribution.
The non-dominant one-third radius, which is a cortical-rich region.
The whole forearm, averaging all available regions.
The dominant ulnar shaft, regardless of the scan indication.
In the controlled ulnar-loading experiment described in the text, which change was observed in loaded regions?
A universal increase in serum calcitonin.
Loss of all osteocytes from the bone.
Reduced osteocyte Sost expression and sclerostin staining.
Direct measurement of Wnt activity by clinical DXA.
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