The Bath metrology index as assessed by a trained and an untrained rater in patients with spondylarthropathy: a study of intra- and inter-rater agreements.

The Bath ankylosing spondylitis metrology index (BASMI; range 0-10) has gained widespread use in daily clinical practice as an objective measure of spinal stiffness not only in patients with ankylosing spondylitis (AS) but also in patients with other spondylarthropathies (SpA). We examined intra-rater and inter-rater reproducibility of BASMI scoring in 30 Danish patients with SpA (median age 40 years, range 22-56 years) fulfilling the European Spondylarthropathy Study Group criteria, 25 of them satisfying the modified New York Criteria for AS. Measurements were performed twice on two different days (median interval 7 days, range 4-11) by a trained physiotherapist (PT) and by an untrained nurse who had undergone a single 1-h training session with the PT. The median BASMI score obtained by the PT on the two test days was 3.5 (range 1-8) and 3.0 (range 1-8), respectively (NS). Test-retest BASMI scores from the PT were significantly correlated (r(s) = 0.95, p < 0.0001). The 95% likely range for the difference between a patient's BASMI scores from two tests was +/-1.4 corresponding to a minimal detectable difference of +/-2 in the individual patient as the scale consists of intervals of 1. Similar results were achieved by the nurse. BASMI scores obtained by the two raters were significantly inter-correlated (r(s) = 0.95, p < 0.0001). The mean difference between paired BASMI scores obtained by the nurse and the PT on test day 1 was -0.2 with a minimal detectable difference of +/-2. A similar result was found using data from test day 2. In conclusion, a change in BASMI less than 2 may be due solely to expected random measurement error. A single 1-h training session allowed an untrained nurse to obtain BASMI results almost identical to those of an experienced PT.

Bone status in rheumatoid arthritis assessed at peripheral sites by three different quantitative ultrasound devices.

Rheumatoid arthritis (RA) is characterized by periarticular and generalized loss of bone mass. Quantitative ultrasound (QUS) has been introduced as a method for the assessment of bone status and fracture risk. In this cross-sectional study bone status was assessed by QUS at different peripheral sites in 27 women with RA (mean disease duration 15 years) and in 36 healthy women matched for age, height and weight. Speed of sound (SOS, m/s), broadband ultrasound attenuation (BUA, dB/MHz) and stiffness of the calcaneus were assessed by a Lunar Achilles device. Amplitude-dependent SOS (Ad-SOS, m/s) of the second to fifth phalanx was measured by a DBM Sonic 1200, and SOS of the distal forearm and third phalanx was measured by a Omnisense multisite scanner. Bone mass (g/cm2 or g) of the hip, spine, distal forearm and total body was measured by dual-energy X-ray absorptiometry. QUS values were significantly reduced in RA at most sites ( p<0.005-0.001), but between-group differences were small, and large overlaps between the groups were noticed. After correction for bone mass, the observed differences remained statistically significant for the calcaneus and distal radius ( p<0.05). Independent associations between ultrasound measures and markers of disease activity were not demonstrated. In conclusion, bone status as assessed by QUS was compromised in RA, but whether ultrasound transmission may serve as a marker of disease progression and fracture risk in the individual patient remains to be clarified in prospective studies.

Bone quality and bone mass as assessed by quantitative ultrasound and dual energy x ray absorptiometry in women with rheumatoid arthritis: relationship with quadriceps strength.

OBJECTIVE: To examine relationships of bone quality as assessed by quantitative ultrasound (QUS) and bone mineral density (BMD, g/cm(2)) with quadriceps strength (QS) in women with rheumatoid arthritis (RA). METHODS: Sixty seven women with RA according to the 1987 American College of Rheumatology (ACR) criteria were examined. Mean (SD) age was 62 (13) years, mean disease duration 15 years. Most were or had been receiving glucocorticoid treatment. Calcaneal bone quality expressed as speed of sound (SOS, m/s), broadband ultrasound attenuation (BUA, dB/MHz), and stiffness was measured by QUS. BMD of the femoral neck, spine, and distal forearm was measured by dual energy x ray absorptiometry (DXA). Maximal voluntary isokinetic quadriceps strength (Nm) was assessed by isokinetic dynamometry. Pain was recorded on a visual analogue scale (VAS), disability was scored by the Stanford Health Assessment Questionnaire (HAQ), and the degree of physical impairment was expressed by the Steinbrocker index (SI). RESULTS: In multiple regression analyses, QS predicted SOS, BUA, and stiffness (r(partial) ranging from 0.36 to 0.45, p<0.005) and femoral neck BMD (r(partial)=0.30, p<0.05) independently of age, height, weight, disease duration, HAQ, VAS, SI, and cumulative steroid dose. BMD of the spine and distal forearm was not associated with QS. After adjustment for covariates, women with subnormal BMD of the femoral neck (T score <-1), had a 20% lower QS than those with normal BMD (p<0.0001). CONCLUSIONS: Calcaneal bone quality and femoral neck BMD were associated with QS in women with RA. This finding indicates that physical activity including muscle strengthening exercises may play a part in the prevention of bone loss in these patients.

Associations of isokinetic knee extensor and flexor strength with steroid use and walking ability in women with rheumatoid arthritis.

Seventy-five women with rheumatoid arthritis according to the 1987 criteria of the American Rheumatism Association were examined. Mean age was 61.9 +/- 12.5 years, mean disease duration 14 years. Sixty-three were or had been on steroids (median cumulative prednisolone dose 2.5 g). Maximal voluntary knee extensor and flexor strength (Nm) was assessed at 30 degrees/s by an isokinetic dynamometer. Walking ability was expressed as walking and stair-climbing time (s). Markers of disease activity included number of swollen and tender joints, pain as recorded by the patients on a visual analogue scale (VAS), and disability as scored by the Stanford Health Assessment Questionnaire (HAQ). Muscle strength, walking time (50 m) and stair-climbing time were reduced on average by 30%, and increased by 28% and 54% (p<0.0001), respectively, compared to 67 age-, weight- and height-matched healthy women. Associations between muscle strength and cumulative or current steroid dose were not found after correction for age and disease duration. Significant linear correlations were found between knee extensor strength and walking time (r =-0.78, p<0.0001) and stair-climbing time (r = -0.76, p<0.0001). Similar correlations were found for flexor strength. The correlations remained significant (Rpartial ranging from -0.64 to -0.69, p<0.0001) in multiple regression analyses adjusting for age, height, weight, disease duration, number of swollen and tender joints, and VAS and HAQ scores. In conclusion, negative effects of steroids on muscle strength were not demonstrated. Leg muscle strength is an important and independent determinator of walking ability in RA.

Effects of silicone breast prostheses on the assessment of body composition by dual-energy X-ray absorptiometry.

We examined the influence of silicone breast prostheses on body composition as assessed by dual-energy X-ray absorptiometry (DXA). Eighteen women were measured with and without a pair of silicone breast prostheses placed on the upper part of the trunk simulating endogenous implants. Bone area, bone mineral content (BMC), areal bone mineral density (BMD), lean tissue mass (LTM) and fat tissue mass (FTM) of the total body and of the subregions of the body, i.e. the head, trunk, arms and legs, were measured by a Norland XR-36 DXA scanner. After application of the silicone prostheses, bone area, BMC and BMD of the total body significantly increased by an average of 3.7, 6.6 and 3.4% (P<0.0001), respectively. Total body LTM and FTM were not affected. In the trunk region, changes were more pronounced. Trunk BMC, for example, was overestimated by 17.9% (P<0. 0001). The prostheses also influenced measurements of truncal soft tissue composition, with a small but statistically significant overestimation of both LTM (1.1%) and FTM (2.1%) (P<0.05). No changes in bone mass and soft tissue composition were seen in the head, arms and legs. Activation of a high-density detection software utility provided by the manufacturer had no influence on any of the measurements. We conclude that silicone breast prostheses affect the assessment of body composition by DXA.

Influence of orthopaedic metal and high-density detection on body composition as assessed by dual-energy X-ray absorptiometry.

We examined the influence of orthopaedic material and computerized high-density detection (HDD) on analysis of bone mass and soft tissue composition performed by dual-energy X-ray absorptiometry (DXA). Measurements of total and regional bone area, bone mineral content (BMC), areal bone mineral density (BMD), lean tissue mass (LTM) and fat tissue mass (FTM) were made using a Norland XR-26 DXA scanner with dynamically changing samarium filtration. Twenty-one subjects who were free of metal implants were measured without and with a Biomet femoral prosthesis (titanium) placed on the proximal part of the femoral region. Twenty-one women with an endogenous prosthesis in the proximal femur were measured once. Analyses of tissue composition were performed without and with HDD using software provided by the manufacturer. Measurements were considerably affected by exogenous metal with overestimation of LTM and underestimation of FTM and bone area. BMC and BMD were over- or underestimated depending on the anatomical region. Enabling the HDD mode, values of bone area and tissue mass came closer to the expected values (-metal/-HDD) but were in general still significantly different from these. For the total body, the following significant changes were found after application of metal (+metal/-HDD vs. +metal/+HDD, mean values): bone area -19.8% vs. -6.9%, BMC +1.1% vs. -2.1%, BMD +26.5% vs. +4.7%, LTM +12.4% vs. +3.7%, FTM -15.8% vs. -7.0%. A similar pattern of change in tissue composition and bone area was found for the subregions of the body. Changes in tissue composition after HDD were similar in subjects with exogenous and endogenous metal, indicating that the experimental model was appropriate. In conclusion, measurements of tissue composition were substantially influenced by orthopaedic metal. HDD partly corrected for the artefacts induced by the metal.

Soft tissue composition, quadriceps strength, bone quality and bone mass in rheumatoid arthritis.

OBJECTIVES: To examine differences in soft tissue composition, bone quality, bone mass and quadriceps strength between women with rheumatoid arthritis (RA) and healthy controls. METHODS: 79 women with RA (median disease duration 10 yrs) were studied. Most were or had been on steroids. 67 healthy age-matched women served as controls. The lean tissue mass (LTM) and fat mass (FM) of the total body and of the major body subregions, as well as the bone mineral density (BMD, g/cm2) of the femoral neck, spine (L2-L4) and distal forearm were measured by dual energy x-ray absorptiometry (DXA). Bone quality expressed as the speed of sound (SOS m/sec), broadband ultrasound attenuation (BUA, dB/MHz) and stiffness was assessed by an Achilles ultrasound device, and isometric quadriceps strength by an isokinetic dynamometer. RESULTS: No between-group differences were found for the body mass index (BMI, weight/height2), total or regional percentage fat, LTM and FM. However, women with RA had 20% lower quadriceps strength than controls. BMD at the femoral neck and distal forearm, and SOS, BUA and stiffness were significantly lower in patients than in controls. No difference was found for spine BMD. In the RA group, z-scores for SOS and stiffness were significantly more reduced than those for BMD. Multiple regression analyses indicated negative associations between ultrasound parameters and the cumulative steroid dose. CONCLUSIONS: Reductions in BMD and muscle strength in RA were not accompanied by changes in soft tissue composition, Bone quality assessed by ultrasonography was compromised in RA and may be modified by steroids.

Limited effect of sulphasalazine treatment in reactive arthritis. A randomised double blind placebo controlled trial.

OBJECTIVE: To assess the efficacy and safety of sulphasalazine in reactive arthritis. METHODS: Double blind placebo controlled trial of six months duration comparing sulphasalazine 2-3 g per day (n = 37) with matching placebo (n = 42) in adults with active reactive arthritis (age 19-57 years, median 34). Treatment response was evaluated once a month by changes in erythrocyte sedimentation rate (ESR), pain, peripheral arthritis, tender iliosacral joints, entesopathy, extra-articular manifestations, and working ability. RESULTS: 15 patients in the sulphasalazine group and eight in the placebo group withdrew from the study prematurely. Adverse events, primarily gastrointestinal, were the main reason for withdrawal in the actively treated group. Intention-to-treat analyses showed significant improvements over time in both groups in ESR, pain, and number of swollen joints (P < 0.01). Number of days on sick leave decreased significantly in the sulphasalazine group only (P < 0.01). No significant differences between the two groups were present after six months. Among the patients completing the trial according to protocol, persistent complete remission had occurred within two months in five (23%) of the actively treated, but in no placebo treated patients (P = 0.013). CONCLUSIONS: Sulphasalazine seemed to improve only the very short term outcome of reactive arthritis. The possible beneficial effect of the drug should also be weighed against the risk of adverse events. Although these were mainly mild, almost 25% of the patients in the actively treated group gave up treatment for this reason.

Intermittent intravenous followed by intermittent oral 1 alpha(OH)D3 treatment of secondary hyperparathyroidism in uraemia.

OBJECTIVES: To examine whether intermittent oral 1 alpha(OH)D3 treatment of patients on haemodialysis with secondary hyperparathyroidism (HPT) was able to maintain the marked suppression of PTH, which previously had been induced by an intermittent intravenous administration of 1 alpha(OH)D3. Simultaneously, the effect of the different routes of administration of 1 alpha(OH)D3 on the circulating levels of N- and C-terminal PTH fragments was measured. DESIGN: An open study of patients on chronic haemodialysis. SETTING: Renal division, Rigshospitalet, Copenhagen, Denmark. SUBJECTS: A total of 26 patients started and five patients completed the total protocol. INTERVENTIONS: The treatment protocol was divided into three parts: (i) 1 alpha(OH)D3 administered intravenously for > 300 days; then (ii) 1 alpha(OH)D3 administered orally for 100 days, followed by (iii) 1 alpha(OH)D3 administered intravenously again for another 100 days. 1 alpha(OH)D3 was given three times a week at the end of each dialysis. MAIN OUTCOME MEASURES: Intact PTH, N- and C-terminal PTH. RESULTS: Intact PTH levels were significantly (P < 0.0001) suppressed by 90.4 +/- 3.3% after 56 days of intermittent intravenous 1 alpha(OH)D3 treatment. This degree of suppression remained stable during the following period of oral treatment and did not change further when intravenous treatment was reinstituted. The circulating levels of intact PTH and N- and C-terminal iPTH were not influenced by the administered route of 1 alpha(OH)D3. CONCLUSIONS: Intravenous 1 alpha(OH)D3 treatment of the secondary HPT in dialysis patients can safely be changed to oral treatment at the time when optimal suppression of PTH has been achieved.

Long-term effects of intravenous 1 alpha (OH)D3 combined with CaCO3 and low-calcium dialysis on secondary hyperparathyroidism and biochemical bone markers in patients on chronic hemodialysis.

The effects of intravenous administration of 1 alpha-hydroxycholecalciferol [1 alpha (OH)D3] in combination with CaCO3 and 'low-calcium dialysis' (1.25 mmol/l) on plasma (p) parathyroid hormone (PTH) and biochemical bone markers (osteocalcin, alkaline phosphatase, procollagen type 1 c-terminal extension peptide) were examined in 54 patients on chronic hemodialysis with either normal or elevated PTH. Increasing doses of 1 alpha (OH)D3 were administered intravenously under careful control of p-Ca2+ and inorganic phosphate. Blood samples were obtained 1 week before the start of treatment and then every 2nd week. 20 patients with initially normal PTH levels (23.5 +/- 4.17 pg/ml) and 34 patients with initially elevated PTH levels (301 +/- 45 pg/ml) were followed for up to 88 weeks. The present investigation: demonstrated: (1) 'Low-calcium hemodialysis' (1.25 mmol/l) made it possible to use larger doses of CaCO3 and to reduce the doses of an aluminium-containing oral phosphate binder. A decrease in p-Ca2+ during dialysis was induced, and special care had to focus on the compliance to CaCO3, in order not to aggravate the secondary hyperparathyroidism. (2) The combination of 'low-calcium hemodialysis', CaCO3, and pulse intravenous 1 alpha (OH)D3 prevented the development of secondary hyperparathyroidism in patients with normal PTH levels and induced a long-term suppression of p-PTH (106 +/- 25 pg/ml, 88 weeks) in the patients with secondary hyperparathyroidism. By careful monitoring, severe hypercalcemia and hyperphosphatemia were avoided. There were no indications, clinically or biochemically, of development of adynamic bone disease. (3) Bone lesions were healed and a decrease of the bone mineral content in lumbar spine and femoral neck of patients with both normal and elevated PTH levels prevented. (4) The present results may suggest that PTH might be of influence on that regulation of procollagen type 1 c-terminal extension peptide.

Patients with rheumatoid arthritis benefit from early 2nd line therapy: 5 year followup of a prospective double blind placebo controlled study.

OBJECTIVE: To compare 2 treatment strategies in a prospective 5 year study of patients with rheumatoid arthritis (RA): early treatment with slow acting antirheumatic drugs (SAARD) versus a "wait and see" attitude. METHODS: One hundred thirty-seven patients with RA of < 2 years' duration entered a double blind placebo controlled study: patients in the "early" (E) group were treated with auranofin within one year of diagnosis of RA, and SAARD treatment in the initially placebo treated group was delayed 8 months compared with the former group. [The results after 2 years clearly favored early treatment (Borg G, Allander E, Lund B, et al: J Rheumatol 1988; 15:1747-54)]. RESULTS: After a total observation period of 5 years in 75 representative patients, continued improvement in the E group was demonstrated, and differences between the 2 groups were maintained with regard to clinical variables, outcome measures, and radiographic evaluation. CONCLUSION: The results indicate the existence of a therapeutic window in RA within the first 2 years of the disease.

Isometric and isokinetic quadriceps strength in gonarthrosis; inter-relations between quadriceps strength, walking ability, radiology, subchondral bone density and pain.

Patients with osteoarthrosis suffer from disability and pain. We measured isokinetic and isometric peak torque in 20 women with gonarthrosis (GA) and in 26 healthy controls. Relationships between muscle strength, walking and stair climbing time, pain level and pain disability scores as assessed by the patients using an extensive questionnaire, radiological changes and subchondral sclerosis expressed as bone mineral density (BMD, g/cm2) of the proximal tibia were studied. Precision errors of the torque measurements in both GA patients and controls were approximately 6%. In the GA patients, isokinetic and isometric quadriceps strength was reduced by 40 and 15% (p < 0.01) respectively, and walking and stair climbing time was increased by 30% (p < 0.005). Isokinetic strength was a better predictor of pain level and pain disability scores than isometric strength and radiological stage. Walking time and stair climbing time were not associated with quadriceps strength, pain level, pain disability scores or radiological changes. Subchondral BMD was not predictive of pain. The study suggests that quadriceps strength assessed by isokinetic dynamometry in GA is a reliable measurement. Isokinetic strength was pronouncedly reduced compared to isometric strength and was a more important predictor of pain and pain disability than isometric strength. These findings should be taken into consideration when planning exercise studies and programmes in GA.

Bone mineral distribution of the proximal tibia in gonarthrosis assessed in vivo by photon absorption.

Regional bone mineral density (BMD, g/cm2) of the proximal tibia including the subchondral plate was measured in vivo by dual photon absorptiometry (DPA). Twenty-one women and six men with gonarthrosis (GA) were examined. Twenty-four healthy women served as controls for the women. The precision error of the BMD measurements ranged from 1.4-3.7% depending on the region measured. Subchondral BMD correlated significantly to the radiologic stage (P < 0.05). Compared to the controls, BMD of the subchondral plate, BMD of the medial condyle, the medial to lateral distribution ratio of subchondral BMD and the ratio between BMD of the subchondral plate and of the immediately underlying region were significantly increased in patients with predominantly medial GA (P < 0.05-0.0001). The BMD of the lateral condyle was lower in GA patients than in controls (P < 0.05). In patients with unilateral GA, the above-mentioned changes were found in the affected tibia compared to the normal knee in the same individual (P < 0.05). In contrast to any of the patients with varus deformity, the two patients with valgus deformity had higher BMD of the lateral condyle than of the medial. No differences in BMD of the distal forearm or the ultradistal region of the proximal tibia were found between the GA patients and the controls. The study shows that regional bone changes of the proximal tibia in GA can be measured precisely and noninvasively in vivo by DPA.

Relationship between quadriceps strength and bone mineral density of the proximal tibia and distal forearm in women.

It is well known that there is a relationship between muscle strength and bone density, but it is uncertain whether this relationship is site specific. The aim of this study was to assess the relationship of quadriceps strength to site-specific bone mineral density (BMD) of the tibia and to BMD of the forearm. In 66 healthy women, aged 21-78 years, BMD was measured in the proximal tibia and the distal forearm by dual-photon absorptiometry. Isometric and isokinetic strength of the quadriceps was measured using an isokinetic dynamometer (Cybex II). Highly significant correlations between BMD of the proximal tibia and quadriceps strength were found (RS ranging from 0.79 to 0.84, p < 0.0001). Also, BMD of the distal forearm was correlated with quadriceps strength (RS ranging from 0.59 to 0.62, p < 0.0001). In a stepwise multiple regression analysis, quadriceps strength was a better predictor of tibial BMD than age, body height, or weight. However, age, height, and weight were more predictive of forearm BMD than quadriceps strength. When studying the pre- and postmenopausal women separately, quadriceps strength was correlated with BMD of the proximal tibia but not to forearm BMD. In conclusion, the study provides support for a site-specific relationship between muscle and bone.

Hydroxychloroquine and sulphasalazine alone and in combination in rheumatoid arthritis: a randomised double blind trial.

OBJECTIVES: To compare the effects of hydroxychloroquine and sulphasalazine alone and in combination in rheumatoid arthritis. METHODS: A six month randomised, multicentre, double blind trial with three parallel groups was performed. Ninety one outpatients with active rheumatoid arthritis were included. Monthly assessments of erythrocyte sedimentation rate, morning stiffness, number of swollen joints, a pain score, and global assessments were carried out. Radiographs of hands and wrists were taken before and after the trial. RESULTS: Sixty two patients completed the study. The 29 withdrawals caused no evident bias, and there was no difference in side effects among the three groups. All variables improved significantly with time. Patients treated with a combination of hydroxychloroquine and sulphasalazine responded better and faster than those treated with hydroxychloroquine alone, but there was no statistically significant difference between the combination treatment and single drug treatment with sulphasalazine or between treatment with hydroxychloroquine and sulphasalazine given alone. CONCLUSION: The present results do not support a recommendation to use a combination of hydroxychloroquine and sulphasalazine in the treatment of rheumatoid arthritis.

The diagnostic and prognostic value of serum bone Gla protein (osteocalcin) in patients with recurrent breast cancer.

Serum bone Gla protein (S-BGP), a marker of bone metabolism, was measured in 60 patients included in a staging programme for recurrent breast cancer. Other diagnostic procedures comprised S-alkaline phosphatase (S-AP), bone scan (B-scan), bilateral iliac crest bone marrow biopsies, and radiological bone survey. The sites of recurrence were bone (61%), bone marrow (46%), soft tissue (52%), lung (13%), pleura (11%), liver (4%), and brain (2%). Radiology and bone biopsy served as key diagnoses as to the presence or absence of bone metastases. The diagnostic efficiency of B-scan and S-AP was greater than that of S-BGP, and the result of BGP measurement was associated with neither extent nor number of bone metastases. However, the BGP values were significantly lower in patients who had visceral metastases, and the median duration of survival after recurrence was 13 months for patients with low S-BGP levels (= < 2.0 nmol l-1), compared to 18 months for patients with medium S-BGP values (2.0-2.9 nmol l-1), and 25 months for patients with high values (> 3.0 nmol l-1) (p = 0.19). Analyses of the simultaneous effect of univariate prognostic factors were performed using the Cox proportional hazards model. S-alkaline phosphatase (S-AP) and S-BGP were the only significant, independent prognostic factors.

Bone mass and turnover in fibromyalgia.

Physical inactivity accelerates bone loss. Since patients with fibromyalgia are relatively physically inactive, bone mass and markers of bone metabolism were determined in 12 premenopausal women with fibromyalgia and in healthy age matched female control subjects. No differences were found in lumbar bone mineral density, femoral neck bone mineral density, serum levels of alkaline phosphatase, osteocalcin, ionized calcium and phosphate. The urinary excretion of both hydroxyproline and calcium relative to urinary creatinine excretion was significantly higher in patients with fibromyalgia, p = 0.01. This was linked to lower urinary creatinine excretion (p = 0.02) probably reflecting lower physical activity in the patients with fibromyalgia. We conclude that bone mass and turnover are generally not affected in premenopausal women with fibromyalgia.

Long-term suppression of secondary hyperparathyroidism by intravenous 1 alpha-hydroxyvitamin D3 in patients on chronic hemodialysis.

The effect of intravenous 1 alpha-hydroxyvitamin D3 [1 alpha(OH)D3] on circulating levels of intact parathyroid hormone (PTH 1-84) and COOH-terminal immunoreactive PTH(PTH 53-84) was examined in 13 patients on chronic hemodialysis. Thirteen patients were treated for 300 days (10 months), 9 patients for 520 days (14 months) and 6 patients for 720 days (2 years) with increasing doses of 1 alpha(OH)D3 intravenously under careful control of plasma Ca2+. Blood samples were obtained 1 week before start of treatment and then at every 2nd week. None of the patients had previously been treated with oral vitamin D metabolites. Intact PTH levels were maximally suppressed after 27-33 weeks of treatment by approximately 73%. At the end of the study periods, PTH 1-84 was still suppressed by 78 +/- 4.3% after 300 days, 78 +/- 8.8% after 520 days and 85 +/- 6.5% after 720 days. Plasma Ca2+ was kept within normal levels, but showed an initial increase from 1.14 +/- 0.03 to 1.27 +/- 0.15 mmol/l, and an adjustment of the doses of 1 alpha(OH)D3 was necessary. The present investigation demonstrated (1) that intravenous administration of the 1-hydroxylated vitamin D metabolite 1 alpha(OH)D3 induced a significant decrease in circulating levels of biologically active intact PTH, and (2) that it was possible to maintain the marked suppression of PTH secretion by intravenous treatment of 1 alpha (OH)D3 for up to 2 years. Hypercalcemia could be avoided by careful monitoring of plasma Ca2+ and adjustment of the doses of 1 alpha(OH)D3.