CHAPTER 31

Metabolic bone disease

Timothy Cundy  •  Ian R. Reid  •  Andrew Grey

CHAPTER OUTLINE

BONE BIOLOGY  604 BONE DISEASE IN PRIMARY

Anatomy of bone  604 HYPERPARATHYROIDISM  628
Bone matrix proteins  605 Clinical, biochemical and histological
Cellular elements of bone  607 features  628
Biochemical markers of bone turnover  609 Treatment  629

OSTEOPOROSIS  613 PAGET DISEASE OF BONE  629

Causes of osteoporosis  614 Epidemiology  629
Investigation and diagnosis  615 Aetiology  629
Treatment  617 Natural history  629
Pathology  630
OSTEOMALACIA  620
Clinical features  630
Calciopenic osteomalacia  620
Investigations  630
Phosphopenic osteomalacia  622
Responses to treatment  631
Osteomalacia and acidosis  623
Defective osteoblast function and BONE TURNOVER AND BONE DISEASE
osteomalacia  623 IN CHILDREN  632
CHRONIC KIDNEY DISEASE – MINERAL AND GENETIC BONE DISEASES  632
BONE DISORDER  624 Osteogenesis imperfecta  632
Aetiology  624 High bone mass  634
Clinical features  625 Other disorders  634
Investigations  625
CONCLUSION  634
Treatment  627
Bone disease after renal transplantation  628 APPENDICES  635

BONE BIOLOGY elements of bone can be packed together without inter-

The principal role of the skeleton is a structural one,
maintaining body shape, providing protection for inter-
nal organs and, together with the neuromuscular system,
making locomotion possible. It also has an important
secondary role in mineral homoeostasis, functioning as
a reservoir for calcium ions in particular. Metabolic bone
diseases can affect both these functions.
Anatomy of bone
Macroscopic
The anatomist classifies bones as being either flat (e.g.
skull, scapula, mandible, ilium) or long (e.g. the limb
bones). Flat bones result from intramembranous ossifi-
cation; long bones predominantly from endochondral
ossification. A long bone consists of a shaft (diaphysis)
broadening at either end into an epiphysis. The transi-
tional zone between the diaphysis and the epiphysis is
termed the metaphysis. On sectioning a long bone, two
patterns of organization of bone tissue are found. The
vening marrow spaces to form cortical or compact bone,
or they can form an interlacing meshwork of trabeculae
referred to as cancellous or trabecular bone. The diaph-
ysis of the long bone consists mainly of cortical bone,
whereas the metaphysis and epiphysis have a greater
quantity of trabecular bone, enclosed within a thin corti-
cal envelope. Some 80% of the weight of an adult human
skeleton consists of cortical bone. However, the surface-
to-volume ratio of trabecular bone is very much higher
than that of cortical bone and it is metabolically much
more active.
Microscopic
At a microscopic level, bone consists of matrix (~35% by
volume), mineral (~60%) and cells (<5%). The matrix is
predominantly type I collagen fibres, usually organized
in layers within which the fibres are parallel to one an-
other. In adult bone, the fibre orientation varies from
one layer to the next and this is referred to as lamellar
bone. If deposited along a flat surface, the lamellae will
be parallel to that surface, but in cortical bone they are

604