Trip Answers

Question answered:30/04/08

ATTRACT found no guidelines discussing this issue and limited research, showing conflicting results, to support decision making in this area.

 

A 2006 review on Congenital Adrenal Hyperplasia in adults (1) has a section on bone density in CAH which states:

 

“Osteoporosis has been an understandable concern for adults with CAH who are glucocorticoid dependent. Corticosteroid therapy inhibits osteoblastic activity, which potentially leads to decreased bone density. Similarly, markers of bone formation, especially osteocalcin, are reported to be low in adult CAH.

There are no data regarding fracture risk in subjects with CAH. Table 1 summarizes eight papers measuring surrogate markers of bone integrity in subjects with CAH. Five studies show normal bone mineral density (BMD) with the expected decline with age. Several studies suggested that low BMD in CAH reflects overtreatment with glucocorticoid, resulting in an increased steroid effect on bone and, to a lesser degree, to an oversuppression of androgens, which can be bone protective. However, other studies found no association between BMD and duration of steroid treatment. In the 36 individuals attending the Middlesex Clinic who have had BMD measurements, we found mean t-scores for the lumbar spine and hip (–0·55 and –0·48, respectively) were not significantly lower than a normal comparison group and that BMI and glucocorticoid dose were not significantly associated with the measurement.

The overall conclusion is that, despite lower serum concentrations of bone turnover markers, bone density is normal in most individuals with CAH. Preservation of bone integrity despite glucocorticoid use may have several explanations. The raised BMI common in CAH may be protective for bone. Furthermore, episodes of androgen excess may have an anabolic effect on bone. However, it is important to note that, when measured, androgen levels were generally lower in both men and women with CAH than that found in control groups. It is likely that current treatment strategies provide close to physiological replacement of glucocorticoid, therefore avoiding the effects of supraphysiological doses of these medications on bone.

In summary, unless there is a clinical suspicion of previous over-treatment with glucocorticoids, routine bone density measurements are not necessary in the young adult with CAH. If there is evidence of significant glucocorticoid overtreatment, one baseline BMD measurement is probably justified. Currently there is insufficient information on older subjects with CAH; one study included three older female subjects and another two, while none included older male subjects. Until we have more data in this age group, it seems prudent to consider bone density measurements in those subjects over the age of 40.”

Table 1 is available in the PDF document at http://www.blackwell-synergy.com/doi/abs/10.1111/j.1365-2265.2005.02410.x

Since this review was published, ATTRACT found a 2007 study of 61 women, aged 18-63 yr, with genetically verified CAH due to 21-hydroxylase deficiency (1). They were patients with salt wasting (n = 27), simple virilizing (n = 28), and nonclassical 21-hydroxylase deficiency (n = 6). A total of 61 age-matched women were controls. The abstract states

“MAIN OUTCOME MEASURES: History of fractures was recorded. Total body, lumbar spine, and femoral neck BMD were measured by dual-energy x-ray absorptiometry. The World Health Organization criteria for osteopenia and osteoporosis were used. Serum marker of bone resorption, beta-C telopeptide was studied. RESULTS: The mean glucocorticoid dose in hydrocortisone equivalents was 16.9 +/- 0.9 mg/m2. Patients had lower BMD than controls at all measured sites (P < 0.001). In patients younger than 30 yr old, 48% were osteopenic vs. 12% in controls (P < 0.009). In patients 30 yr or older, 73% were osteopenic or osteoporotic vs. 21% in controls (P < 0.001). BMD was similar in the two classical forms and had no obvious relationship to genotypes. beta-C-telopeptide was decreased in older patients. More fractures were reported in patients than controls (P < 0.001). The number of vertebrae and wrist fractures almost reached significance (P = 0.058).”

One other study from 2006 investigated bone effects in thirty young patients with the classical form of CAH (aged 16.4-29.7 yr) treated with glucocorticoid from diagnosis (duration of treatment 16.4-29.5 yr) and 138 healthy controls (aged 16.0-30.0 yr) were enrolled (2). The abstract states:

“MAIN OUTCOME MEASURES: BMD was measured in the lumbar spine and whole body by dual-energy x-ray absorptiometry. Bone formation and resorption rates were estimated by serum measurements of bone-specific alkaline phosphatase and C-terminal telopeptide of type I collagen, respectively. RESULTS: CAH patients were shorter than controls (women -6.8 and men -13.3 cm). Therefore, several methods were used to account for the effect of this difference on bone measurements. Whole-body BMD measurements were significantly lower, compared with controls (P < 0.03), after controlling for height (on average -2.5% in females and -9.3% in male patients). No differences were found in lumbar spine measurements. Bone-specific alkaline phosphatase and C-terminal telopeptide of type I collagen serum concentrations were higher in CAH patients than control subjects (P < 0.04). BMD measurements and bone metabolism markers did not correlate with the actual glucocorticoid dose or mean dose over the previous 7 yr.”

 

1.  Ogilvie CM et al, Congenital adrenal hyperplasia in adults: a review of medical, surgical and psychological issues. Clinical Endocrinology (2006). 64,2.

http://www.blackwell-synergy.com/doi/abs/10.1111/j.1365-2265.2005.02410.x

2.  Falhammar H, Fractures and bone mineral density in adult women with 21-hydroxylase deficiency. J Clin Endocrinol Metab. 2007 Dec;92(12):4643-9.

 

3. Sciannamblo M, Reduced bone mineral density and increased bone metabolism rate in young adult patients with 21-hydroxylase deficiency. J Clin Endocrinol Metab. 2006 Nov;91(11):4453-8.

 

---

DISCLAIMER: TRIPanswers is a collection of clinical questions and answers.  Each provider will have their own methodology in answering questions and these are likely not to be as rigorous as systematic review.  If you have any doubt as to the implications of this contact the Q&A Service Provider for further information. This document is presented for information purposes only. This document cannot and should not be used as a basis of diagnosis or choice of treatment, and is in no way intended to replace professional medical care or attention by a qualified practitioner. TRIPanswers and TRIP Database Ltd are not responsible or liable for, directly or indirectly, ANY form of damage whatsoever resulting from the use/misuse of information contained in or implied by this document.  Also, ensure you have read the terms and conditions for using the site.