Page 786 - Basic _ Clinical Pharmacology ( PDFDrive )

42 Agents That Affect Bone
C H A P T E R

Mineral Homeostasis

Daniel D. Bikle, MD, PhD

C ASE STUD Y

A 65-year-old man is referred to you from his primary care Examination shows kyphosis of the thoracic spine, with
physician (PCP) for evaluation and management of pos- some tenderness to fist percussion over the thoracic spine.
sible osteoporosis. He saw his PCP for evaluation of low The dual-energy x-ray absorptiometry (DEXA) measure-
back pain. X-rays of the spine showed some degenerative ment of the lumbar spine is “within the normal limits,” but
changes in the lumbar spine plus several wedge deformities the radiologist noted that the reading may be misleading
in the thoracic spine. The patient is a long-time smoker because of degenerative changes. The hip measurement
(up to two packs per day) and has two to four glasses of shows a T score (number of standard deviations by which
wine with dinner, more on the weekends. He has chronic the patient’s measured bone density differs from that of
bronchitis, presumably from smoking, and has been treated a normal young adult) in the femoral neck of –2.2. What
on numerous occasions with oral prednisone for exacerba- further workup should be considered, and what therapy
tions of bronchitis. He is currently on 10 mg/d prednisone. should be initiated?

■ BASIC PHARMACOLOGY been implicated as an endocrine tissue with release of osteocalcin,
which in its uncarboxylated form stimulates insulin secretion and
Calcium and phosphate, the major mineral constituents of bone, testicular function. Abnormalities in bone mineral homeostasis
are also two of the most important minerals for general cellular can lead to a wide variety of cellular dysfunctions (eg, tetany,
function. Accordingly, the body has evolved complex mecha- coma, muscle weakness), disturbances in structural support of the
nisms to carefully maintain calcium and phosphate homeostasis body (eg, osteoporosis with fractures), and loss of hematopoietic
(Figure 42–1). Approximately 98% of the 1–2 kg of calcium and capacity (eg, infantile osteopetrosis).
85% of the 1 kg of phosphorus in the human adult are found in Calcium and phosphate enter the body from the intestine. The
bone, the principal reservoir for these minerals. This reservoir is average American diet provides 600–1000 mg of calcium per day,
dynamic, with constant remodeling of bone and ready exchange of which approximately 100–250 mg is absorbed. This amount
of bone mineral with that in the extracellular fluid. Bone also represents net absorption, because both absorption (principally
serves as the principal structural support for the body and pro- in the duodenum and upper jejunum) and secretion (principally
vides the space for hematopoiesis. This relationship is more in the ileum) occur. The quantity of phosphorus in the American
than fortuitous, as elements of the bone marrow affect skeletal diet is about the same as that of calcium. However, the efficiency
processes just as skeletal elements affect hematopoietic processes. of absorption (principally in the jejunum) is greater, ranging from
During aging and in nutritional diseases such as anorexia nervosa 70% to 90%, depending on intake. In the steady state, renal
and obesity, fat accumulates in the marrow, suggesting a dynamic excretion of calcium and phosphate balances intestinal absorp-
interaction between marrow fat and bone. Furthermore, bone has tion. In general, more than 98% of filtered calcium and 85% of

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