long-term change in the bone mineral density of adults with adult onset growth hormone (gh)...

Clinical Endocrinology (1998) 48, 463–469

463q 1998 Blackwell Science Ltd

Long-term change in the bone mineral density of adultswith adult onset growth hormone (GH) deficiency inresponse to short or long-term GH replacement therapy

A. Rahim*, S. J. Holmes*, J. E. Adams† andS. M. Shalet**Department of Endocrinology, Christie Hospital,Wilmslow Road, Withington, Manchester and†Department of Diagnostic Radiology, University ofManchester, Oxford Road, Manchester, UK

(Received 23 June 1997; returned for revision 31 October 1997;finally revised 17 November 1997; accepted 5 December 1997)

Summary

OBJECTIVE Only two previous studies haveassessed the effects of long-term GH replacementtherapy on bone mineral density (BMD) in patientswith adult onset GH deficiency. To date no study haslooked at the long-term impact on BMD after a shortcourse (6–12 months) of GH replacement. In twogroups of patients with adult onset GH deficiencywe have studied BMD either (a) after 3 years ofcontinuous GH replacement or (b) 2 years aftercompletion of a short course of GH.DESIGN An open GH therapeutic study in whichpatients were recruited from a previous double-blindplacebo-controlled study. The BMD status of allpatients was unknown to the physician and patientat the time of recruitment.PATIENTS Group A ( n ¼ 7, three females) all receivedGH replacement continuously for 3 years. Group B(n ¼ 8, five females) included six patients whoreceived GH replacement for 6 months and two whoreceived GH replacement for 12 months with BMDbeing measured at 6-monthly intervals.METHODS Single photon absorptiometry (SPA) andlater single X-ray absorptiometry (SXA) were used tomeasure forearm cortical BMD. Dual-energy X-rayabsorptiometry (DXA) was used to measure lumbarspine, trochanteric, femoral neck and Ward’s areaBMD.RESULTS In group A lumbar spine and trochanterBMD had increased significantly from baseline by3·7% (DXA: median change ¼ 0·045 g/cm2; P ¼ 0·028)

and 4·0% (DXA: median change ¼ 0·031 g/cm2;P ¼ 0·046), respectively. There were non-significantdecreases in femoral neck (1·9%) (DXA: medianchange ¼ ¹ 0·02 g/cm2; P ¼ 0·39), Ward’s area (6·5%)(DXA: median change ¼ ¹ 0·06 g/cm2; P ¼ 0·09) andforearm (2·6%) (SPA/SXA: median change ¼ ¹ 0·013g/cm 2; P ¼ 0·18). In group B, compared with baseline,only trochanter BMD changed significantly, increas-ing by 5·9% (DXA: median change ¼ 0·0485 g/cm2;P ¼ 0·049). Lumbar spine (DXA: median change ¼

¹0·001 g/cm2) Ward’s area (DXA: median change ¼

0·0135 g/cm2), femoral neck (DXA: median change ¼

¹0·005 g/cm2) and forearm cortical (SPA/SXA; medianchange ¼ ¹ 0·01 g/cm2) BMD did not change signifi-cantly ( P ¼ 0·67, P ¼ 0·57, P ¼ 0·86 and P ¼ 0·31,respectively). Median percentage changes comparedwith baseline were ¹0·1%, 1·8%, ¹0·5% and ¹2·1%,respectively. From the time of completion of GHtherapy however, BMD increased significantly atlumbar spine, (median change ¼ 0·023 g/cm2), Ward’sarea (median change ¼ 0·03 g/cm2) and trochanter(median change ¼ 0·056 g/cm2) (P ¼ 0·036, P ¼ 0·049and P ¼ 0·012, respectively) but not at the femoralneck (median change ¼ 0·017 g/cm2; P ¼ 0·31) orforearm (median change ¼ 0 g/cm 2; P ¼ 0·75).CONCLUSION Long-term GH replacement therapy forthree years appears to have beneficial effects on bonein patients with adult onset GH deficiency particularlyat the lumbar spine and trochanter; the effects onfemoral neck and forearm cortical BMD, however,are less impressive. A short course (6–12 months)of GH replacement therapy results in an increase introchanter BMD several years later, and after an initialdecline in BMD whilst on GH replacement, lumbarspine and Ward’s area BMD return towards their base-line values. These results emphasize that not all typesof bone and skeletal sites respond to GH therapyidentically. Furthermore a short course of GH replace-ment over 6–12 months may result in significantchanges in BMD several years later.

Growth hormone deficiency (GHD) in adults, whether adult(Rosen et al., 1993; Holmeset al., 1994) or childhood(Kaufman et al., 1992; O’Halloranet al., 1993) onset, is

Correspondence: Professor S. M. Shalet, Department ofEndocrinology, Christie Hospital NHS Trust, Wilmslow Road,Manchester M20 4BX, UK.

associated with reduced bone mineral density (BMD). This is ofclinical significance as it is well established that bone mineralcontent and density correlate with the risk of fractures (Wasnichet al., 1985; Huiet al., 1989; Meltonet al., 1993). In a recentretrospective study using questionnaires, Rose´n et al. (1995)estimated the fracture rate in 89 hypopituitary patients with GHdeficiency compared with an age-matched control group andfound a 2-fold increase in fracture rate in both male and femalepatients with GH deficiency. These latter observations (Rose´net al., 1995) fit well with the predicted risk of fracture in adultswho have a BMD standard deviation score (SDS) of¹1, as seenin the adult GH deficient patient population (O’Halloranet al.,1993; Holmeset al., 1994).

One argument for GH replacement therapy in GH-deficientadults is the possible beneficial effect on bone mass and hencereduced risk of fractures in later life. We have previouslystudied the effects of 6 and 12 months GH replacement in adultswith childhood (O’Halloranet al., 1993) and adult (Holmeset al., 1995a) onset GH deficiency with contrasting results. Inthe former group, 6 months of replacement therapy resulted in asignificant increase in spinal trabecular BMD measured byquantitative computed tomography (QCT), with the increasemaintained at 12 months. Proximal forearm (cortical) bonemineral content (BMC) and distal forearm (cortical andtrabecular) BMC, measured by single photon absorptiometry(SPA), increased significantly only after 12 months ofcontinuous GH replacement. In contrast the response of BMDto 6 and 12 months of GH replacement in adult onset GHdeficiency has been disappointing. Six months of GH replace-ment resulted in a significant decrease in BMD at the forearm,lumbar spine and femoral neck. After 12 months of GHreplacement there was a significant decrease in lumbar spineBMD from baseline. This decrease in lumbar spine BMD maybe of consequence to those continuing therapy and also thosepatients who decline long-term GH therapy after a shortempirical trial (6–12 months) (Holmes & Shalet, 1995).Osteopenic GH-deficient adults may be reluctant to embarkon an empirical trial of 6–12 months GH therapy if there is apotential risk of increasing the degree of osteopenia.

To date no study has assessed BMD in patients with adultonset GH deficiency after 3 years of continuous replacementtherapy or once GH therapy has ceased. We have assessedBMD in two groups of patients after either 3 years’ continuousGH (group A;n= 7) or 2 years after completing a 6–12-monthcourse of GH replacement (group B;n= 8).

Patients and method

Patients

Group A (n= 7; three females) received 3 years of continuousGH replacement and BMD was assessed at 6-monthly intervals.

Group B (n= 8; five females) received GH replacement foreither 6 or 12 months and, following completion of GHreplacement, had assessment of BMD at yearly intervals for 2years. All patients had adult onset GH deficiency and had beenGH deficient for at least 2 years. The diagnosis of GHdeficiency was made on the basis of a peak serum GH responseof less than 9 mU/l to provocative testing with either insulin-induced hypoglycaemia, arginine stimulation or glucagonstimulation; 11 patients had a peak GH response of less than5 mU/l. None of the patients had received treatment with GHprior to the study.

The most common pathological lesion was a pituitaryadenoma (n= 9). The remaining pathology consisted of twopinealomas, one meningioma, one glioma, one hamartoma ofthe third ventricle and one craniopharyngioma. All 15 patientshad previously received irradiation to a field which included thehypothalamic–pituitary axis and 12 patients had previouslyundergone hypothalamic–pituitary surgery.

In group A, two patients had isolated GH deficiency. One ofthese received bromocriptine throughout the study period forhyperprolactinaemia. Of the remaining five patients all receivedglucocorticoid, four with hydrocortisone and one cortisoneacetate, and sex steroids. Four of the five patients receivedthyroxine and one patient also received desmopressin throughoutthe study period.

In group B, two patients had isolated GH deficiency. Onepatient was post-menopausal and receiving sex steroid replace-ment. Of the remaining patients all were gonadotrophin-deficientand all except one female, aged 57 years at entry into the study,were receiving sex steroid replacement. Three patients wereACTH deficient, with two receiving hydrocortisone and oneprednisolone and, of these three, one also had TSH deficiencyand was receiving thyroxine. Replacement therapy remainedunaltered throughout the study period. All patients had beenreceiving stable hormone replacement therapy for theirpituitary hormone deficits at least 6 months before entry intothe present study. All patients had previously taken part in astudy looking at the changes in BMD at various sites after 6 and12 months GH replacement therapy (Holmeset al., 1995a). Atthe time the decision was made to take part in the present studyneither monitoring clinician nor patient were aware of the BMDresults.

During the first month of the study patients self-administeredsubcutaneous GH at a dose of 0·125 IU/kg body weight/week.After 4 weeks this was increased to 0·25 IU/kg body weight/week with a maximum daily dose of 4 IU/day. All patients onGH therapy received at least 95% of their daily GHinjections.

Serum IGF-I levels were measured at baseline and then 6-monthly while patients were receiving GH replacement. Allsamples were taken in the morning from fasting patients.

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q 1998 Blackwell Science Ltd,Clinical Endocrinology, 48, 463–469

Bone mineral measurements

DXA. Measurement of integral bone was made in the lumbarspine (L2–L4) and the right proximal femur (femoral neck,Ward’s area and trochanteric region) using a Lunar DPX-L(Lunar Corporation, Madison, Wisconsin, USA) (Callumet al.,1989), and using software Version 1.1 and age- and sex-matched reference data provided by the manufacturer. MeanBMD was measured in g/cm2. Precision of the measurement inour department is 0.5% in the spine, 2.5% in the femoral neck,3% in the trochanter and 6% in Ward’s area.

SPA and SXA. Initially bone mineral measurement wasperformed in the non-dominant forearm using a Nuclear DataND1100A scanner with a125I radionuclide source (Wahneret al.,1977). For technical reasons forearm measurements had to bechanged to single X-ray absorptiometry (SXA), using theOsteometer DTX-100 scanner (Osteometer MediTech A/S,Roedovre, Denmark), during the study. Cross-calibrationstudies (n= 96 subjects) confirmed that the cortical BMDmeasurements made by either SPA or SXA were directlyequivalent (r = 0.98;P<0.0001; mean slope 1.0; mean intercept¹0.02 (Adamset al., unpublished observation). Scanning wasperformed at the proximal site, giving a measure of corticalbone. BMC was measured in g/cm. Bone width (BW) wasmeasured at the proximal site and was used to provide a measureof BMD (BMC/BW, measured in g/cm2). Precision of BMDmeasurement by both SPA and SXA is 1% at the proximal site.

Serum assays

IGF-I. Serum IGF-I concentration was measured by Pharmacia-Upjohn Ltd (Stockholm, Sweden) using an in-house radio-immunoassay. At an IGF-I concentration of 202mg/l theintra-assay and inter-assay CVs were 3·1 and 10.0%, respec-tively. Cross-reactivity of the assay for IGF-II was 1% and forinsulin and proinsulin was negligible.

Statistics

Statistical analyses were performed using nonparametric tests.The Mann–WhitneyU-test was used to compare bone mineralmeasurements at baseline in the two groups of patients. Therewere no significant differences in BMD at any site assessedbetween patients who had received either 6 (n¼ 2) or 12 (n¼ 6)months of GH replacement at completion of GH therapy or atcompletion of the study period. The two subgroups weretherefore combined for the purpose of statistical analysis.Friedman’s test was used to determine whether there were anysignificant differences between BMD at baseline, i.e. beforeGH replacement therapy was started, and 3 years later in group

A and 2 years after completion of GH replacement therapy ingroup B. Wilcoxon’s signed-rank matched-pairs test was usedsubsequently to determine between which measurements anysignificant differences existed. This test was also used tocompare IGF-I concentrations. AP value of less than 0·05 wasconsidered statistically significant.

Results

Group A

The median (range) age, weight and BMI in group A were 42(27–59) years, 84 (66–106) kg and 28 (24–39) kg/m2,respectively.

Lumbar spine BMD decreased significantly after treatmentfor 1 year (P¼ 0·018). After 3 years of continuous therapy withGH, lumbar spine BMD and trochanter BMD had increasedsignificantly from baseline by 3·7% (DXA: median change¼

0·045 g/cm2; P¼ 0·028) and 4·0% (DXA: median change¼

0·031 g/cm2; P¼ 0·046), respectively. After GH therapy for 1year, the lumbar spine BMDZ-score (BMD compared with ageand sex-matched reference data) decreased from a median(range) at baseline of¹1·08 (¹1·65–0·54) to¹1·24 (¹1·67–0·47). After 3 years of continuous therapy, however, the median(range)Z-score had increased to¹0·59 (¹1·22–0·93).

Femoral neck BMD decreased non-significantly by 1·9%(DXA: median change¼ ¹ 0·02 g/cm2; P¼ 0·39). Despite thisnon-significant decrease in femoral neck BMD, theZ-scoreactually increased from a median (range) of 0·31 (¹0·41–2·13)at baseline to 0·47 (¹0·61–1·86) at 3 years. Ward’s area BMDhad decreased by 6·5% (DXA: median change¼ ¹ 0·06 g/cm2)but this did not reach significance (P¼ 0·09). Over the 3-yearperiod there was a great deal of variation in changes in BMD atall sites measured by DXA. Forearm cortical BMD decreased

Long-term changes in BMD after short- or long-term GH replacement 465


0.1

00.8

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Lumbar spine

Ward's Femoral neck

Trochanter Forearm

–0.2

–00.4

–00.6

–00.8

–0.1

∆ B

MD

g/c

m2

Fig. 1 Changes in BMD from baseline to 36 months in group A.

by 2·6% (SPA/SXA: median change¼ ¹ 0·013 g/cm2) (Fig. 1).This change however, did not reach statistical significance(P¼ 0·18). The median (range)Z-score for forearm corticalBMD also decreased from¹0·09 (¹1·27–1·00) to¹0·59(¹4·64–0·1) (age-matched reference data were not available inone patient).

Group B

The median (range) age, weight and BMI in group B were 42(34–63) years, 73 (58–117) kg and 28 (22–39) kg/m2,respectively.

In group B, compared with baseline, only trochanter BMDchanged significantly, increasing by 5·9% (DXA: medianchange¼ 0·0485 g/cm2; P¼ 0·049). Lumbar spine (DXA:median change¼ ¹ 0·001 g/cm2) Ward’s area (DXA: medianchange¼ 0·0135 g/cm2), femoral neck (DXA: medianchange¼¹ 0·005 g/cm2) and forearm cortical (SPA/SXA:median change¼ ¹ 0·01 g/cm2) BMD did not change signifi-cantly (P¼ 0·67,P¼ 0·57,P¼ 0·86 andP¼ 0·31, respectively).Median percentage changes compared with baseline were¹0·1%, 1·8%,¹0·5% and¹2·1%, respectively. Compared withbaseline, the median (range) lumbar spine BMDZ-score haddecreased marginally from¹0·7 (¹2·2–0·59) to ¹0·77(¹1·89–0·83) 2 years after completion of GH therapy.Although femoral neck BMD decreased, the median (range)femoral neck BMDZ-score actually increased over the sametime period from¹0·41 (¹1·58–3·02) to¹0·19 (¹1·19–3·14).

From completion of GH therapy, however, BMD increasedsignificantly at lumbar spine (median change¼ 0·023 g/cm2)Ward’s area (median change¼ 0·03 g/cm2) and trochanter(median change¼ 0·056 g/cm2) (P¼ 0·036, P¼ 0·049 andP¼ 0·012, respectively) (Fig. 2). The percentage medianchange at the femoral neck after completion of GH replacement

therapy was 1·2% but this change did not reach statisticalsignificance (DXA: median change¼ 0·017 g/cm2; P¼ 0·31).Forearm cortical BMD was unaltered (SPA/SXA: medianchange¼ 0 g/cm2).

In group A the median (range) serum IGF-I SD scores (Fig. 3)at baseline and 6 months were¹2 (¹5·08–1·09) and 2·3(¹3·87–5·4), respectively. In group B the median (range)serum IGF-I SD scores at baseline and 6 months were¹0·85(¹1·5–1·1) and 1·85 (¹1·76–5·17) respectively. At 6 monthseight of the 15 subjects had serum IGF-I SD scores greater thanþ2.

No relationship between theZ-score at baseline and theresponse to GH replacement at any skeletal site was observed.Analysis of the data from different sites revealed norelationship between the changes in BMD within an individual,i.e. those showing a reduction in BMD at one site did notnecessarily show a decrease at any other site.

Discussion

Adult patients with adult (Johanssonet al., 1992; Bing-Youetal., 1993; Rose´n et al., 1993; Holmeset al., 1994) or childhood(Degerbaldet al., 1990; Hyeret al., 1992; Kaufmanet al., 1992;O’Halloran et al., 1993; De Boeret al., 1994) onset GHdeficiency are osteopenic compared with the normal popula-tion. There is evidence that the BMD deficit of patients withadult onset isolated GH deficiency and multiple pituitaryhormone deficiencies is similar (Holmeset al., 1994),suggesting that GH plays a role in the maintenance of BMDin adulthood.

The present study demonstrates that 3 years of continuousGH replacement therapy results in a significant increase inlumbar spine and trochanter BMD with no significant change in

466 A Rahim et al.


0.11

0.02

0.05

Lumbar spine

Ward's

Trochanter

Femoral neck

Forearm

0.08

–0.11

–0.02

–0.05

–0.08

∆ B

MD

g/c

m2

Fig. 2 Changes in BMD 24 months after completion of a6–12-month course of GH therapy (group B).

6

4

2

0

–2

–4

–60 6 12 18

Time (months)

24 30 36

IGF

-I S

D s

co

re

Fig. 3 Serum IGF-I SD scores during the study period (X group A,O group B).

Ward’s area or femoral neck BMD. Several other studies haveassessed the changes in BMD in patients with adult-onset GHdeficiency in response to GH therapy (Bengtssonet al., 1993;Rosen et al., 1994; Stiegler & Leb, 1994; Beshyahet al., 1995;Holmes et al., 1995a; Baumet al., 1996; Johannssonet al.,1996; Weaver et al., 1996). The therapeutic study byJohannssonet al. (1996) has been of the longest duration,with patients receiving GH for 2 years. In 44 patients withadult-onset GH deficiency, Johannssonet al. (1996) demon-strated a 3·8%, 5·6%, 4·1% and 4·9% increase in lumbar spineL2–L4, femoral trochanter, femoral neck and Ward’s areaBMD, respectively. At GH doses similar to those used byJohannssonet al. (1996) we demonstrated an increase in thelumbar spine and trochanter BMD with the percentage changesbeing of similar degree (3·7% and 4%, respectively) butoccurring with 3 years’ continuous GH replacement. Themedian lumbar spine BMDZ-score also increased, supportingincrease in bone mass. At the femoral neck and Ward’s area weobserved a non-significant decrease in BMD. Despite thisdecrease in femoral neck BMD the medianZ-score at this siteincreased, suggesting a reduction in the rate of decline infemoral neck bone mass.

Forearm cortical BMD and medianZ-score decreased aftercontinuous GH therapy, as did Ward’s area BMD. Thisdecrease was disappointing, particularly in forearm corticalBMD, as long-term GH therapy might be expected to result inan increase in BMD at this site; particularly as we (O’Halloranet al., 1993) have previously shown an increase in forearmcortical BMC in young adults with childhood-onset GHdeficiency after GH therapy for 1 year, followed by a furtherincrease in forearm cortical BMC the year after stopping GH(Holmeset al., 1995b).

The different response of forearm bone from that at thelumbar spine, femoral neck and trochanter may be due to thetype of bone in these regions. The measurement in the forearmis of cortical bone; at the other sites integral bone is measuredwith varying proportions of cortical and trabecular bone. Fromhistomorphometric studies (Schnitzleret al., 1996) in normalsubjects it is known that there is a structural difference at thecellular level between the axial and appendicular skeleton. Theresponse of bone to GH may therefore be dependent on the typeof bone predominating at the site being assessed. Longerfollow-up is required to assess the impact of continued GHtherapy on forearm cortical BMD.

The present study demonstrates variations in BMD measure-ments at all sites at different times. This is illustrated in thegroup on continuous GH replacement therapy and is probablydue to several factors which have recently been discussed byNguyen (1997) and colleagues. Variability may be due to theeffects of GH replacement on the bone remodelling cycle butalso to subject positioning and measurement technique,

variation due to biological changes (such as body composition,state of hydration) over time in any individual and biologicaldifferences between individuals. These variations are alsogreater in sites in which the degree of precision is known to beless when compared with the spine and femoral neck.

A significant decrease in lumbar spine BMD was noted at 1year. This may be due to several factors. First, there is areduction in lumbar spine BMD due to an initial increase inbone remodelling space before new bone formation. Completebone formation and mineralization may then take a further 6–12 months. Secondly, changes in body composition result indecreased soft tissue over the lumbar spine. This may result infalse reduction in lumbar spine BMD using DXA (Bengtssonet al., 1993; Tothillet al., 1994). Finally, the dose of GH used inthe first year of the study may influence BMD changes.Balducci et al. (1995) hypothesized that relatively high-doseGH may result in greater osteoclast than osteoblast activity;markers of bone resorption, urinary hydroxyproline/creatinineratio, remain elevated while markers of bone formation,osteocalcin and alkaline phosphatase return to pretreatmentlevels in patients on high-dose GH, suggesting that boneremodelling may become unsychronized with bone resorptionpredominating (Balducciet al., 1995). Baumet al. (1996)studied the effects of physiological GH replacement as judgedby serum IGF-I in men with adult-onset GH deficiency; 32 menwere studied and a significant increase in lumbar spine andfemoral neck BMD occurred after 18 months’ GH therapy.These data advance the case for physiological GH replacementand emphasize the possible deleterious effects of using higherdoses. The IGF-I data in the present study clearly suggest over-treatment in the first year of the study, when GH wasadministered at a standard dose related to body weight. IGF-Istandard deviation scores (SDS) were above, or at least at theupper end, of the normal range during this period. After the firstyear GH replacement was titrated using the IGF-I SDS and, at36 months, in those who continued with GH replacement, theIGF-I SDS had returned to lie around the upper end of thenormal range implying a more physiological replacement dose.However, the IGF-I SDS remained greater thanþ2 in threepatients.

Only one study has looked at BMD after discontinuation ofGH replacement (Holmeset al., 1995b). Reassessment of bonemass 1 year after completion of a 12-month course of GHreplacement in 10 adult patients with childhood-onset GHdeficiency demonstrated a further increase in forearm corticalBMC but no significant change in forearm integral BMC orvertebral trabecular BMD. As forearm bone width did notincrease significantly over this time period, this suggested thatthe increase in cortical BMC was due to a persisting effect ofprevious GH replacement therapy through the bone remodellingcycle.



Several studies (Binnertset al., 1992; Whiteheadet al., 1992;Amato et al., 1993; Thorenet al., 1993; Beshyahet al., 1995;Stiegler & Web, 1994; Balducciet al., 1995; Holmeset al.,1995a) have demonstrated a decrease in BMD following a shortcourse (3–6 months) of GH replacement but none has assessedBMD after a period off GH. In the present study we havedemonstrated changes in BMD up to 2 years after completion ofa short course of GH therapy. Compared with baseline, 2 yearsafter completion of a short course of GH, there was nosignificant change in BMD, except at the trochanter whereBMD increased by almost 6%. Femoral neck BMD decreasedover the same time period but, as in group A, the medianZ-score for the femoral neck increased from baseline. Two yearsfrom completion of GH treatment, however, a significantincrease at lumbar spine, Ward’s area and trochanter BMD wasobserved. Femoral neck BMD and medianZ-score alsoincreased, although this change did not reach significance.These changes suggest that having exposed bone to exogenousGH, initiation of the bone remodelling cycle is triggered and,once initiated, each cycle is then completed regardless offurther or continued exposure to GH. This is reassuring,particularly as the earlier studies had shown that a short courseof GH replacement resulted in a decrease in BMD (Binnertset al., 1992; Whiteheadet al., 1992; Amatoet al., 1993;Thoren et al., 1993; Stiegler & Web, 1994; Balducciet al.,1995; Beshyahet al., 1995; Holmeset al., 1995a).

In summary, we have shown that GH replacement therapy for3 years results in significant increases in lumbar spine andtrochanter BMD and also reduces the rate at which the femoralneckZ-score decreases. Two years after completion of a shortcourse (6–12 months) of GH replacement therapy, a significantincrease in trochanter BMD was observed and after an initialdecline in BMD while on GH replacement, lumbar spine,Ward’s area and femoral neck BMD returned towards theirbaseline values. When considering the impact of GH therapy onBMD a number of variables need to be considered, whichinclude the dose of GH administered, the type of bone (cortical,trabecular or integral in the appendicular or axial skeleton)being assessed and the variability in repeated measures atdifferent time points in the same individual.

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long-term change in the bone mineral density of adults with adult onset growth hormone (gh)...

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