172 Arthritis and Musculoskeletal Conditions
progressive condition, there remains great variability in the
subjective experience of the disease. Some patients with radi-
ographically con“rmed advanced disease report few symp-
toms, whereas some patients with mild but detectable disease
activity report a great deal of pain and activity limitation
(Pincus et al., 1984). Thus, the biopsychosocial diathesis fac-
tors discussed in this chapter may serve as moderators of the
relationship between radiographic evidence of joint damage
and the person•s experience.
As in RA, there exist many epidemiological and clinical
risk factors for the development and prognosis of OA. First,
the prevalence of OA increases dramatically with age
(Lawrence et al., 1998). However, there is evidence that
younger individuals with OA suffer from more psychological
disability and pain, whereas older individuals experience
more physical disability (Weinberger, Tierney, Booher, &
Hiner, 1990). This “nding underscores the importance of
considering psychosocial in addition to biological factors
when evaluating OA prognosis. Second, although women are
at greater overall risk, men and women are vulnerable to dif-
ferent forms of OA. For instance, women tend to develop
knee and hand OA whereas men are more likely to develop
hip OA (Lawrence et al., 1998; Mankin, 1993). Furthermore,
women are more likely than men to develop generalized OA,
which is a more widespread form of OA. Thus, gender ap-
pears to affect the clinical presentation of OA.
In addition to epidemiological risk factors, there also exist
clinical risk factors for OA. Among these are skeletal struc-
ture abnormalities and obesity (Kraus, 1997). The role of
these risk factors for development of OA is best understood
with a diathesis-stress approach. For instance, neither skele-
tal structure abnormalities nor obesity alone is suf“cient for
development of OA. Instead, these clinical risk factors may
interact with one another to produce OA. For example, an in-
dividual with a congenital skeletal structural abnormality
may not develop OA unless he or she experiences an injury
or stresses a structurally vulnerable joint with a lifetime of
excess weight.
Genetic in”uences are not limited to RA. In OA, genetics
have been hypothesized to in”uence dif ferent aspects of
the disease process. For instance, results of some studies in-
dicate that individuals with OA inherit genes that either
change the consistency of the cartilage (thus making it
more vulnerable to destruction) or produce greater levels of
cartilage-destroying enzymes (for review, see Kraus, 1997).
Additionally, there appear to be genetic in”uences on the
type of OA that individuals develop. There is strong evidence
for a genetic in”uence on development of hand, spine, and
generalized OA (Bijkerk et al., 1999; Felson et al., 1998).
However, while genetics may increase the risk of developing
OA, these genetic risk factors alone are not suf“cient to
produce OA.FibromyalgiaFM is a chronic pain syndrome of unknown origin that cur-
rently affects an estimated 3.7 million Americans. In contrast
to the physical evidence of disease processes in RA and OA,
individuals with FM experience chronic musculoskeletal
pain with no identi“able site of pathology. Despite the lack of
identi“able pathology, numerous researchers have attempted
to understand the biological processes in FM. One of the
most viable models for FM is a dysregulation of neuro-
hormonal and pain-transmitting substances in the central
nervous system (CNS) (for a review, see Bennett, 1999). An
imbalance of crucial pain-transmitting chemicals such as
substance P (Russell et al., 1994) and dysregulation of HPA
axis activity have been documented in patients with FM
(Adler, Kinsley, Hurwitz, Mossey, & Goldenberg, 1999;
Bennett, 1999; Catley, Kaell, Kirschbaum, & Stone, 2000;
Clauw & Chrousos, 1997). The “nding that the majority of
individuals with FM report nonrefreshing sleep provides fur-
ther evidence for CNS dysregulation in FM (Bennett, 1993).
In healthy individuals, stage 3 and 4 sleep is characterized
by delta-wave activity. However, results of early studies on
sleep patterns in FM patients revealed that the delta-wave
activity of stages 3 and 4 sleep were consistently interrupted
by the alpha waves normally found in stage 1 and stage
2 (Moldofsky, Scarisbrick, England, & Smythe, 1975).
Furthermore, when healthy individuals were selectively de-
prived of stage 4 sleep for several days, they began to com-
plain of musculoskeletal pain and fatigue (Moldofsky &
Scarisbrick, 1976). Although the alpha-delta sleep abnormal-
ity is not speci“c to FM, as it has been observed in individu-
als without FM, it may represent a source of vulnerability to
development of FM under favorable circumstances, espe-
cially considering that stage 4 sleep is a time of neurohor-
monal and neurotransmitter restoration (Bennett, 1993).
Unlike OA and RA, which are diseases that affect the
joints, FM is characterized by widespread pain in soft tissue.
Pain appears to be particularly noxious at speci“c •tender
pointsŽ distributed throughout the body. To receive a diagno-
sis of FM, an individual must experience widespread pain in
all four quadrants of the body and especially pronounced pain
in at least 11 of 18 •tender pointŽ spots (Wolfe et al., 1990).
Other common symptoms of FM include fatigue, stiffness,
and depression (Bennett, 1993; Wolfe et al., 1990).
There remains considerable controversy surrounding the
course and prognosis for this condition. Although FM symp-
toms tend to be chronic, there is substantial individual