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347
For complex cases such as being unable to use standard medications or with
concurrent CKD, a rheumatologist familiar with transplant recipients should be
consulted. Patients with urate nephropathy or more advanced CKD should also have
a nephrologist involved in their care.
11.7 Osteoporosis
11.7.1 Epidemiology
Osteoporosis is a frequent metabolic complication in solid organ transplant recipi-
ents, who have a vefold increased risk compared to patients without a solid organ
transplant [63]. The prevalence of osteoporotic fractures in solid organ transplant
recipients has been reported as high as 65% [64], although it appears to be decreas-
ing in recent years, perhaps due to greater awareness, prevention (e.g., reduced use
of glucocorticoids), and treatment. Lung transplant recipients appear to have a
higher risk for osteoporosis than other solid organ transplant recipients, likely
related to extensive exposure to glucocorticoids both pre and post-transplant [63].
11.7.2 Pathophysiology
Solid organ transplant recipients often have both pre- and post-transplant risk fac-
tors for decreased bone mineral density. Pre-transplant risk factors include compli-
cations of the specic disease states leading to organ failure: e.g., altered bone
mineral metabolism in patients with chronic kidney and liver disease and reduced
calcium and vitamin D absorption in patients with cystic brosis; as well as general
factors such as malnutrition, malabsorption, secondary hypogonadism, decreased
weight bearing exercise, low body weight, and exposure to alcohol or tobacco.
Additionally, many transplant candidates have had extensive exposure to glucocor-
ticoids prior to transplant [65].
The rate of bone loss appears to be greatest in the rst 6–12months after solid
organ transplantation [66] and is related to both nonpharmacologic and pharmaco-
logic causes. These include complications of surgery itself, such as acute and
chronic kidney injury, as well as decreased mobility and nutrition in the event of
extensive post-surgical hospitalization and lengthy rehabilitation courses. However,
the most dominant post-transplant risk factor for osteoporosis is the medication
used for immunosuppression. Glucocorticoids, which rapidly decrease bone density
in doses as low as prednisone 2.5mg per day [67] by directly inhibiting osteoblast
bone building activity and stimulating osteoclast bone resorptive activity, are often
used in high doses during the rst 6months after transplant. Calcineurin inhibitors
including cyclosporine and tacrolimus have also been shown to decrease bone
11 Metabolic Complications intheAdult Solid Organ Transplant Recipient
348
density in animal models by stimulating osteoclast bone resorptive activity [68],
although quantifying this risk has been more challenging to study in solid organ
transplant recipients who often receive glucocorticoids in combination with CNIs.
Additionally, CNIs often cause kidney injury that further adversely impacts bone
metabolism.
The rate of bone density loss appears to slow after the rst post-transplant year,
likely due to decreased immunosuppressive medication dosing as well as improved
mobility and nutritional status.
11.7.3 Screening
Some professional transplant society guidelines and transplant experts recommend
screening for osteoporosis, prevalent fractures, and low serum 25-hydroxy vitamin
D level as part of the pre-transplant evaluation to help guide prevention of further
bone density loss and fractures in the peri and post-transplant period. Similarly,
society guidelines also recommend regular surveillance bone mineral density
(BMD) evaluation with dual-energy X-ray absorptiometry (DXA), with frequency
varying based on type of transplant, immunosuppressant pharmacologic regimen,
and baseline BMD (see Table 14.3 in Chap. 14).
11.7.4 Prevention
As with other patients at risk for osteoporosis, solid organ transplant recipients
should be counseled on lifestyle measures to decrease the rate of BMD decline and
fall risk including avoiding tobacco, excess alcohol, and engaging in regular weight
bearing activity. Additionally, professional transplant society guidelines recom-
mend that all solid organ transplant recipients take adequate calcium (1000–1200mg
daily through diet and supplements) and vitamin D (400–1000IU daily or higher if
needed to achieve serum 25-OH D levels >20 to30ng/mL) [15, 69, 70]. However,
the various societies differ in their recommendations for who should receive pro-
phylactic anti-resorptive therapy (see Table 14.3 in Chap. 14). The International
Society for Heart and Lung Transplantation (ISHLT) takes the most aggressive
approach, recommending that antiresorptive therapy should be considered for all
heart transplant recipients during the rst post-transplant year [69]. For kidney
transplant recipients, prophylactic and treatment considerations are more nuanced
as BMD does not reliably predict fracture risk or type of bone disease in this popula-
tion. Kidney transplant practice guidelines recommend frequent monitoring of
serum calcium, phosphorus, PTH, and 25-OH Vitamin D as well as consideration of
bone biopsy prior to bisphosphonate use to inform mechanism of low bone mineral
density and optimal treatment [71].
A. L. Golob et al.
349
11.7.5 Treatment
Osteoporosis-specic medical therapy is recommended for solid organ transplant
recipients with either pre- or post-transplantation osteoporosis, dened as either a T
score ≤−2.5 or a history of an osteoporotic (fragility) fracture [65]. All solid organ
transplant recipients being treated for osteoporosis should also take adequate cal-
cium (1000–1200mg daily in divided doses, either through diet or supplement) and
vitamin D (400–1000IU daily; or sufcient to maintain serum 25 hydroxy vitamin
D levels above 30 ng/mL) [65]. Modiable risk factors such as alcohol use and
smoking should be addressed.
Similar to the general population, bisphosphonates are the most used rst-line
osteoporosis prevention and treatment agents for solid organ transplant recipients
who do not have contraindications such as advanced kidney disease (eGFR <30mL/
min/1.73m
2
), high-risk dental disease, or, for oral bisphosphonates, dysphagia. This
practice is based primarily on multiple prevention-focused trials that demonstrated
decreased rates of bone loss, increasing bone mineral density, and/or decreased
fractures in SOT recipients treated with bisphosphonates for the rst year after
transplant [72]. 25 hydroxy vitamin D levels should be checked and repleted if
found to be low prior to starting bisphosphonate therapy. Caution should be taken in
premenopausal female solid organ transplant recipients with preserved fertility as
bisphosphonates are contraindicated in pregnancy.
As per above, the evaluation and treatment of osteoporosis in kidney transplant
recipients is more nuanced given the high prevalence of adynamic bone disease
related to longstanding kidney disease. In this population, KDIGO recommends
consideration of bone biopsy prior to initiating bisphosphonates [71].
Second-line evidence-based options to treat osteoporosis in solid organ trans-
plant recipients who are not candidates for bisphosphonates include calcitriol, estro-
gen/progesterone in hypogonadal premenopausal women, or testosterone therapy in
hypogonadal men. Calcitriol has been shown to reduce rate of bone loss and prevent
fractures in solid organ transplant recipients [72]. If calcitriol is used, it is important
to monitor for hypercalcemia regularly; and either stop calcium supplements or
reduce or stop the calcitriol if the hypercalcemia persists.
Other agents that are FDA-approved for the treatment of osteoporosis and are
considered second line ahead of calcitriol and sex hormonal therapy in the general
population, including teriparatide,, denosumab, and romosuzumab unfortunately
have not yet been well studied for use in solid organ transplant recipients, and are
therefore not generally recommended [69].
In general, for patients who do not tolerate or have contraindications to bisphos-
phonate therapy, the primary care provider should consult an endocrinologist or
metabolic bone disease specialist familiar with the care of transplant recipients to
optimize therapy.
There are not consensus guidelines on duration of treatment with osteoporosis-
specic medications in solid organ transplant recipients. Experts recommend
11 Metabolic Complications intheAdult Solid Organ Transplant Recipient
350
individualized management, with regular (every 1–2year) surveillance DXA, and
consideration of changes in the immunosuppressive regimen, other osteoporosis
risk factors, incident fractures, and response to therapy to guide management.
11.8 Conclusion
As the solid organ transplant recipient population both increases and ages, it is key
for primary care providers to become familiar with common metabolic complica-
tions that occur in these patients. A general understanding of the pathophysiology of
these complications, some of which are unique to transplant recipients and some of
which overlap with the general population, as well as specic nuances in their treat-
ment, will aid primary care providers in continuing to promote longevity and quality
of life of their patients long after transplantation.
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355© The Author(s), under exclusive license to Springer Nature
Switzerland AG 2025
C. J. Wong (ed.), Primary Care of the Solid Organ Transplant Recipient,
https://doi.org/10.1007/978-3-031-98076-3_12
Chapter 12
Mental Health intheAdult Solid Organ
Transplant Recipient
GenaLenti, AshwinKarnik, andThomasSoeprono
12.1 Pre-transplant Mental Health
Care of a solid organ transplant recipient’s mental health requires an under-
standing of the typical approach to a patient’s mental health pre-transplant. This
section reviews the prevalence of affective disorders and substance use disor-
ders, the screening process by which a transplant candidate’s psychosocial well-
being is assessed, and what factors may predict mental health and other
psychosocial challenges post-transplant. We will briey discuss pharmacother-
apy considerations pre- transplant as it relates to the need for medication adjust-
ments in the post-transplant setting.
G. Lenti (*)
Department of Medicine, Division of General Internal Medicine, University of Washington,
Seattle, WA, USA
e-mail: glenti@uw.edu
A. Karnik
Department of Psychiatry, University of Washington, Seattle, WA, USA
e-mail: ashwink@uw.edu
T. Soeprono
Consultation Liaison Psychiatry Fellowship Program, Transplant Psychiatry, Department of
Psychiatry, University of Washington, Seattle, WA, USA
e-mail: thomasms@uw.edu
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12.1.1 Prevalence ofAffective Disorders Prior toSolid
Organ Transplant
Patients awaiting solid organ transplant (SOT) experience affective disorders at
higher rates than the general population, for which the CDC reports a lifetime
depression prevalence of 18% [1]. Higher rates of affective disorders can be expected
in the SOT population given the stressors of managing severe chronic disease and
the emotional distress associated with awaiting transplant. Multiple studies have
sought to understand the prevalence of affective disorders in the pre-transplant
phase, though reported prevalence varies depending on measurements used. In a
study of 103 patients who underwent orthotopic liver transplant [2], 41% were
found to have had depression and/or anxiety pre-liver transplant. Rates of affective
disorders may be even more common in those with alcohol related liver disease
(ARLD) compared to those with other chronic liver diseases [3]: the reported preva-
lence of pre-transplant mood disorders in patients with ARLD ranges from 22% to
66% [4–6]. A study of patients on the kidney and liver transplant waiting lists found
that 51.6% of patients (52% of those awaiting kidney transplant, 50% awaiting liver
transplant) exhibited depressive symptoms [7]. Among lung transplant recipients,
40% had a pre-transplant history of depression and 25% had pre-transplant history
of anxiety [8]. The reported prevalence of major depressive disorder in patients on
the heart transplant waiting list is 24% [9].
12.1.2 Pre-transplant Psychosocial andMental
Health Screening
While all transplant screening guidelines require psychosocial assessment, psycho-
social listing criteria and cutoffs are not standardized across transplant centers [10].
Standardized tools have been created to aid in this process. The Stanford Integrated
Psychosocial Assessment for Transplant (SIPAT) is one tool used at many transplant
centers in the United States (US). The SIPAT was designed to assess psychosocial
variables and behaviors that have common negative effects among transplant candi-
dates regardless of organ [10]. The SIPAT more specically assesses four psychoso-
cial domains, including the patient’s readiness for transplant, social support,
psychological stability, and substance use (Table12.1). Patients who are listed for
transplant are often those with lower SIPAT scores, as higher scores were correlated
with poor psychosocial and medical outcomes, such as higher rates of organ rejec-
tion episodes, hospitalizations, and psychiatric decompensation. Risk factors are
additive in that having more risk factors more strongly predicts poor post-transplant
outcomes and may inuence the time to onset of psychiatric symptoms post-
transplant [10].
While psychosocial screening can be variable, tools such as the SIPAT standard-
ize screening and help care teams identify risk factors that may be amenable to
G. Lenti etal.