Diseases affecting bone quality: beyond osteoporosis

Abstract

Background: Bone quantity, quality, and turnover contribute to whole bone strength. Although bone mineral density, or bone quantity, is associated with increased fracture risk, less is known about bone quality. Various conditions, including disorders of mineral homeostasis, disorders in bone remodeling, collagen disorders, and drugs, affect bone quality.

Questions/purposes: The objectives of this review are to (1) identify the conditions and diseases that could adversely affect bone quality besides osteoporosis, and (2) evaluate how these conditions influence bone quality.

Methods: We searched PubMed using the keywords "causes" combined with "secondary osteoporosis" or "fragility fracture." After identifying 20 disorders/conditions, we subsequently searched each condition to evaluate its effect on bone quality.

Results: Many disorders or conditions have an effect on bone metabolism, leading to fragility fractures. These disorders include abnormalities that disrupt mineral homeostasis, lead to an alteration of the mineralization process, and ultimately reduce bone strength. The balance between bone formation and resorption is also essential to prevent microdamage accumulation and maintain proper material and structural integrity of the bone. As a result, diseases that alter the bone turnover process lead to a reduction of bone strength. Because Type I collagen is the most abundant protein found in bone, defects in Type I collagen can result in alterations of material property, ultimately leading to fragility fractures. Additionally, some medications can adversely affect bone.

Conclusions: Recognizing these conditions and diseases and understanding their etiology and pathogenesis is crucial for patient care and maintaining overall bone health.

Fig. 1

The photomicrograph of a patient diagnosed with osteomalacia shows interconnected trabeculae that contains central regions of mineralized bone (#) covered almost completely by an excessive amount of unmineralized osteoid matrix (*). The marrow contents consist of an unremarkable amount of hematopoietic elements and intermixed fat cells (Stain, Goldner trichrome; original magnification, ×10).

Fig. 2A–C

Images of a patient diagnosed with hyperparathyroidism. (A) Radiograph of the right foot shows subperiosteal resorption of the second, third, fourth, and fifth proximal phalanges (white arrowheads) and brown tumor at the distal metaphysis of the fifth metatarsal (*). Note the bone cortices are thin on both sides but remain intact. Courtesy of Bernard Ghelman, MD. (B) The photomicrograph shows thickened trabecula undergoing tunneling resorption with a central defect undergoing reparative activity. Multinucleate osteoclasts are present in resorption bays (black arrowheads). The osteoblasts are present in single cell layers (black arrows) on the smooth surfaces inside the central tunnel and on the marrow surface of the bone (Stain, hematoxylin and eosin; original magnification, ×10). (C) The photomicrograph shows the histologic presentation of brown tumor resulting from secondary hyperparathyroidism. Typical features of brown tumor are seen with osteoclast-like giant cells and foci of microhemorrhage (asterisk) and fibroblastic stroma with hemosiderin (double asterisks) (Stain, hematoxylin and eosin; original magnification, ×20).

Fig. 3A–B

Images of a patient diagnosed with Paget’s disease. (A) AP radiograph of the left proximal femur shows increased width of the femoral shaft, markedly thickened cortices, coarse but disorganized trabeculae, and small lytic areas within the medullary canal. (B) The photomicrograph illustrates the active phase of Paget’s disease with numerous trabeculae undergoing resorption by osteoclasts (arrows) and a thin layer of surface-related osteoblasts (arrowheads). Subsequent osteoblastic activity results in cement lines and the “mosaic” pattern apparent in sclerotic phases (Stain, hematoxylin and eosin; original magnification, ×10).

Fig. 4A–B

Images of a patient diagnosed with osteopetrosis. (A) An AP radiograph of the pelvis shows uniform increased bone density. The trabecular pattern is difficult to identify in the bones, hence the name “marble-bone disease.” The medullary spaces are mostly obliterated. (B) The photomicrograph illustrates thickened and dystrophic trabeculae (pink) containing irregularly shaped central cores and fragments of residual cartilage (blue). Defective osteoclasts lead to abnormal bone remodeling, which precludes repair of local bone damage, resulting in production of abnormal trabecular architecture (Stain, hematoxylin and eosin; original magnification, ×10).

Fig. 5

Radiograph of a patient diagnosed with subtrochanteric femoral fracture attributed to long-term bisphosphonate exposure. Fracture after prolonged treatment with alendronate is characterized by (1) simple or transverse fracture, (2) beaking of the cortex on one side (white arrow), (3) hypertrophied diaphyseal cortices (asterisks), and (4) result from minimal or no trauma.