Structural progression rate decreases over time on serial radiography and magnetic resonance imaging of sacroiliac joints and spine in a five-year follow-up study of patients with ankylosing spondylitis treated with tumour necrosis factor inhibitor.

OBJECTIVE: To investigate temporal changes in structural progression assessed by serial conventional radiography and magnetic resonance imaging (MRI) of the sacroiliac joints (SIJs) and spine in patients with ankylosing spondylitis (AS) treated with tumour necrosis factor (TNF) inhibitor for 5 years. METHOD: Forty-two patients were included and 33 patients were followed for 5 years in a prospective investigator-initiated study. Conventional radiographs were required four times and MRI seven times. The modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS); Spondyloarthritis Research Consortium of Canada (SPARCC) MRI SIJ and Spine Inflammation, and SPARCC MRI SIJ Structural Score (SSS) for Fat, Erosion, Backfill, and Ankylosis; and the Canada-Denmark MRI scores for Spine Inflammation, Fat, Erosion, and New Bone Formation (NBF) were applied. RESULTS: Compared with baseline, MRI Inflammation had decreased significantly at week 22 (spine)/week 46 (SIJ) and thereafter. MRI SIJ Fat (from week 22), SIJ Ankylosis, Spine NBF, and mSASSS had increased significantly at week 46 and thereafter. SIJ Erosion had decreased from year 2. The annual progression rate in mSASSS was significantly higher during weeks 0-46 compared to week 46 to year 3. In multivariate regression analyses, baseline SIJ Inflammation and Backfill were independent predictors of 5 year progression in SIJ Ankylosis. Spine Erosion predicted progression in Spine NBF. Longitudinally, Ankylosing Spondylitis Disease Activity Score, Bath Ankylosing Spondylitis Disease Activity Index, MRI Spine Inflammation, Fat, and Erosion scores were significantly associated with mSASSS. SIJ Inflammation, Fat, Erosion, and Backfill scores were longitudinally associated with SIJ Ankylosis. Structural progression was not associated with body mass index, smoking, or Assessment of SpondyloArthritis international Society Non-Steroidal Anti-Inflammatory Drug Index. CONCLUSION: In a 5 year follow-up study of patients with AS treated with TNF inhibitor, structural progression decreased over time.

A powder made from seeds and shells of a rose-hip subspecies (Rosa canina) reduces symptoms of knee and hip osteoarthritis: a randomized, double-blind, placebo-controlled clinical trial.

OBJECTIVE: The aim of this study was to determine whether a herbal remedy made from a subspecies of rose-hip (Rosa canina) might reduce symptoms of osteoarthritis and consumption of rescue medication in patients suffering from osteoarthritis. METHODS: Ninety-four patients with osteoarthritis of the hip or knee were enrolled in a randomized, placebo-controlled, double-blind crossover trial. Forty-seven patients were given 5 g of the herbal remedy daily for a period of 3 months and the remaining patients were given a similar amount of placebo. The group initially treated with placebo was then changed to rose-hip and vice versa for another 3-month period. Upon inclusion and after 3 weeks and 3 months of each treatment period, pain, stiffness, disability, and global severity of the disease were scored on a Western Ontario and McMaster Universities (WOMAC) questionnaire. After 3 weeks of treatment, patients, if possible, were allowed to reduce their consumption of 'rescue medication'. Data were analysed on the basis of intention to treat. RESULTS: Rose-hip resulted in a significant reduction in WOMAC pain (p<0.014) as compared to placebo, when testing after 3 weeks of treatment. The consumption of 'rescue medication' significantly declined as a result of active treatment (p<0.027). WOMAC disability, stiffness, and global assessment of severity of the disease were not altered by 3 weeks but decreased significantly (p<0.018, p<0.038, and p<0.035, respectively) after 3 months of treatment. CONCLUSION: The data suggest that the present herbal remedy can alleviate symptoms of osteoarthritis and reduce the consumption of 'rescue medication'.

Treatment of knee osteoarthritis with pulsed electromagnetic fields: a randomized, double-blind, placebo-controlled study.

OBJECTIVE: The investigation aimed at determining the effectiveness of pulsed electromagnetic fields (PEMF) in the treatment of osteoarthritis (OA) of the knee by conducting a randomized, double-blind, placebo-controlled clinical trial. DESIGN: The trial consisted of 2h daily treatment 5 days per week for 6 weeks in 83 patients with knee OA. Patient evaluations were done at baseline and after 2 and 6 weeks of treatment. A follow-up evaluation was done 6 weeks after treatment. Activities of daily living (ADL), pain and stiffness were evaluated using the Western Ontario and McMaster Universities (WOMAC) questionnaire. RESULTS: Within group analysis revealed a significant improvement in ADL, stiffness and pain in the PEMF-treated group at all evaluations. In the control group there was no effect on ADL after 2 weeks and a weak significance was seen after 6 and 12 weeks. Significant effects were seen on pain at all evaluations and on stiffness after 6 and 12 weeks. Between group analysis did not reveal significant improvements over time. Analysis of ADL score for the PEMF-treated group revealed a significant correlation between less improvement and increasing age. Analysis of patients <65 years using between group analysis revealed a significant improvement for stiffness on treated knee after 2 weeks, but this effect was not observed for ADL and pain. CONCLUSIONS: Applying between group analysis we were unable to demonstrate a beneficial symptomatic effect of PEMF in the treatment of knee OA in all patients. However, in patients <65 years of age there is significant and beneficial effect of treatment related to stiffness.

Effect of nasal salmon calcitonin on calcium and bone metabolism.

We have investigated the pharmacokinetics and pharmacodynamics of nasal SCT in the dose range of 50-200 IU. When evaluated by AUC, it appeared that the absorption through the nasal mucosa was dose dependent. The resulting plasma levels of SCT were highly variable between individuals. A hypocalcemic effect accompanied by an increase of s-PTH was seen 2-3 hours after administration of a single dose of 200 IU to healthy male adults, but not after administration to postmenopausal women. When evaluated by changes in biochemical markers of bone remodeling nasal SCT 200 IU decreased bone resorption in the magnitude of 15% after a single dose as well as after a multiple daily dosing regimen. No tachyphylaxis of the antiresorptive effect of nasal SCT was noted. The histomorphometric analysis revealed a decrease of erosion depth as the major antiresorptive action on the bone remodeling system of nasal SCT. We were unable to demonstrate an anabolic effect of nasal SCT on bone formation. There was a tendency towards a dose dependent increase in lumbar BMD, but not even in the group receiving 200 IU daily did the increase reach statistical significance when compared to placebo. BMD in the distal forearm as well as in the hip was unaffected by nasal SCT.

Alendronate for the prevention and treatment of glucocorticoid-induced osteoporosis. Glucocorticoid-Induced Osteoporosis Intervention Study Group.

BACKGROUND: Osteoporosis is a common complication of long-term glucocorticoid therapy for which there is no well-proved preventive or restorative treatment. METHODS: We carried out two 48-week, randomized, placebo-controlled studies of two doses of alendronate in 477 men and women, 17 to 83 years of age, who were receiving glucocorticoid therapy. The primary end point was the difference in the mean percent change in lumbar-spine bone density from base line to week 48 between the groups. Secondary outcomes included changes in bone density of the hip, biochemical markers of bone turnover, and the incidence of new vertebral fractures. RESULTS: The mean (+/-SE) bone density of the lumbar spine increased by 2.1+/-0.3 percent and 2.9+/-0.3 percent, respectively, in the groups that received 5 and 10 mg of alendronate per day (P<0.001) and decreased by 0.4+/-0.3 percent in the placebo group. The femoral-neck bone density increased by 1.2+/-0.4 percent and 1.0+/-0.4 percent in the respective alendronate groups (P<0.01) and decreased by 1.2+/-0.4 percent in the placebo group (P<0.01). The bone density of the trochanter and total body also increased significantly in the patients treated with alendronate. There were proportionally fewer new vertebral fractures in the alendronate groups (overall incidence, 2.3 percent) than in the placebo group (3.7 percent) (relative risk, 0.6; 95 percent confidence interval, 0.1 to 4.4). Markers of bone turnover decreased significantly in the alendronate groups (P<0.001). There were no differences in serious adverse effects among the three groups, but there was a small increase in nonserious upper gastrointestinal effects in the group receiving 10 mg of alendronate. CONCLUSIONS: Alendronate increases bone density in patients receiving glucocorticoid therapy.

[Bone loss during low dose glucocorticoid treatment in patients with polymyalgia rheumatica. A double-blind, prospective comparison between prednisolone and deflazacort]. / Knogletab under lavdosis-glukokortikoidbehandling hos patienter med polymyalgia rheumatica. En dobbeltblind, prospektiv sammenligning mellem prednisolon og deflazacort.

The aim of the study was to compare the long term effects of low dosage prednisolone or deflazacort treatment on bone mass in patients with polymyalgia rheumatica. The subjects were 30 patients with newly diagnosed polymyalgia rheumatica, who were allocated to treatment with prednisolone or deflazacort. Bone Mineral Content (BMC) was measured in the lumbar spine (L-BMC) and distal forearm (A-BMC) before treatment and three, six and 12 months after the start of treatment. After three months the decrease in L-BMC was significantly greater in the deflazacort group than in the prednisolone group (p < 0.05), but at six and 12 months there was not a significant difference between the two groups. There was a significant loss of BMC in all patients after 12 months: a 6.4% loss in L-BMC and a 1.8% loss in A-BMC. In conclusion, this low dose study failed to reveal any calcium sparing property of deflazacort compared with prednisolone.

Increased bone mineral density after prolonged electrically induced cycle training of paralyzed limbs in spinal cord injured man.

Spinal cord injured (SCI) individuals have a substantial loss of bone mass in the lower limbs, equaling approximately 50% of normal values in the proximal tibia, and this has been associated with a high incidence of low impact fractures. To evaluate if this inactivity-associated condition in the SCI population can be reversed with prolonged physical training, ten SCI individuals [ages 35.3 +/- 2.3 years (mean +/- standard error [SE]); post injury time: 12.5 +/- 2.7 years, range 2-24 years; level of lesion: C6-Th4; weight: 78 +/- 3.8 kg] performed 12 months of Functional Electrical Stimulated (FES) upright cycling for 30 min per day, 3 days per week, followed by six months with only one weekly training session. Bone mineral density (BMD) was determined before training and 12 and 18 months later. BMD was measured in the lumbar spine, the femoral neck, and the proximal tibia by dual energy absorptiometry (DEXA, Nordland XR 26 MK1). Before training, BMD was in the proximal tibia (52%), as well as in the femoral neck, lower in SCI subjects than in controls of same age (P < 0.05). BMD of the lumbar spine did not differ between groups (P > 0.05). After 12 months of training, the BMD of the proximal tibia had increased 10%, from 0.49 +/- 0.04 to 0. 54 +/- 0.04 g/cm2 (P < 0.05). After a further 6 months with reduced training, the BMD in the proximal tibia no longer differed from the BMD before training (P > 0.05). No changes were observed in the lumbar spine or in the femoral neck in response to FES cycle training. It is concluded that in SCI, the loss of bone mass in the proximal tibia can be partially reversed by regular long-term FES cycle exercise. However, one exercise session per week is insufficient to maintain this increase.

Five years of clinical experience with intermittent cyclical etidronate for postmenopausal osteoporosis.

OBJECTIVE: To evaluate the effects of 120 weeks of intermittent cyclical etidronate on the progression of bone loss and fracture incidence and rate in postmenopausal osteoporotic women after 150 weeks of either etidronate or placebo treatment. METHODS: This was an open label followup study of 37 postmenopausal osteoporotic women enrolled from the earlier 150 week study, 17 from the etidronate group and 20 from the placebo group. Treatment cycles were of oral doses of etidronate 400 mg/day for 2 weeks, followed by a 13 week drug-free period for a total of 120 weeks. All patients received a daily supplement of 0.5 g calcium and 400 U vitamin D. RESULTS: During the earlier 150 week study, mean vertebral bone mineral content increased significantly in the etidronate group by 5.5% (p = 0.013) and decreased by 2.7% (not significant) in the placebo group. After 120 weeks of etidronate treatment in this followup study, patients who had formerly received etidronate experienced an additional 1.4% increase; after 5 years, bone mineral content was 6.9% above the original baseline (p = 0.037). Bone mineral content also increased in the former placebo group during the latter study, up to 5.3% above the original study baseline (not significant). The vertebral fracture rate in the former placebo group decreased significantly, from 103 to 27 per 100 patient-years (p < 0.01), while the fracture rate in the former etidronate group was unchanged (38 and 33 per 100 patient-years). CONCLUSION: Five years of etidronate therapy for postmenopausal osteoporosis results in significant increases in vertebral bone mineral content, and the previously observed reduction in vertebral fracture rate in the etidronate group is maintained during at least 5 years of therapy.

Effect of nasal salmon calcitonin on bone remodeling and bone mass in postmenopausal osteoporosis.

The effect of nasal salmon calcitonin (SCT) on bone has been investigated by densitometry, biochemical markers of bone turnover, and histomorphometry. 62 women (mean age 65 years) who had experienced Colles' fracture after menopause were randomized to receive either nasal salmon calcitonin (SCT) 200 IU or nasal placebo daily for 24 months. All received a daily supplement of 0.5 g calcium. There was a significant increase above baseline in the bone mineral density of the lumbar spine in the SCT group (2.5%; 95% confidence interval 0.9--4.2%) and in the placebo group (1.7%; 95% confidence interval 0.3--3.1%) after 24 months, but the difference between the groups was not significant (0.8%; 95% confidence interval -1.2-3.0%). Serum levels of osteocalcin decreased significantly below baseline in the SCT group, whereas they were unchanged in the placebo group. At months 12 and 24, serum levels of osteocalcin were significantly lower in the SCT group than in the placebo group (p < 0.03). Urinary levels of deoxypyridinoline/creatinine decreased significantly below baseline in the SCT group, whereas only a transient decrease was observed in the placebo group. The differences between the groups were, however, not significant. The erosion depth was significantly lower in the SCT group than in the placebo group after 12 months (median [interquartile range]; 46.9 mu m [10.4] vs. 50.5 mu m [10.7]; p = 0.03), whereas bone volume and activation frequency did not differ between the groups. This study indicates that nasal SCT in a dose of 200 IU daily induces only a minor inhibition of bone resorption and therefore produces only a minor increase in bone mass. Furthermore, it seems that nasal SCT in a dose of 200 IU does not interfere with the recruitment of new bone multicellular units, but preferably decreases ongoing osteoclastic bone resorption.

Changes in bone mass during low dose corticosteroid treatment in patients with polymyalgia rheumatica: a double blind, prospective comparison between prednisolone and deflazacort.

OBJECTIVE: To compare the long term effects of low dosage prednisolone or deflazacort treatments on bone mass in patients with polymyalgia rheumatica. METHODS: Thirty patients with polymyalgia rheumatica were allocated on a random double blind basis to receive treatment with prednisolone or deflazacort. Bone mineral content (BMC) was measured in the lumbar spine and in the distal forearm before treatment and three, six, and 12 months after treatment. RESULTS: At three months the decrease in lumbar BMC and bone mineral density (BMD) was significantly greater in the deflazacort group than in the prednisolone group (p < 0.05), but at six and 12 months there was no difference between the two groups. In all patients after one year there was a significant loss of BMC: a 6.4% loss in lumbar BMC and a 1.8% loss in distal forearm BMC. Loss in lumbar BMC after six months was correlated to the cumulative dose of corticosteroid (r = 0.4; p < 0.05) and was significantly greater in the group of patients who had persisting symptoms of polymyalgia at six weeks, three months, or both, after treatment started (p = 0.05). CONCLUSION: This low dose study failed to reveal any calcium sparing properties of deflazacort compared with prednisolone. Possible explanations for this finding are discussed.

Comparison of a semiquantitative and a quantitative method for assessing vertebral fractures in osteoporosis.

There is no agreed definition for the assessment of vertebral fractures and deformities in patients with osteoporosis. Radiographs of 66 patients randomized for therapy with etidronate or placebo were analyzed at baseline and during follow-up (60/120/150 weeks) independently using two procedures. The first method of spinal deformity index (SDIG) and vertebral deformity score (VDSG) is based on a semiquantitative visual reading of each vertebra between T4 and L4. The second method of spine deformity index (SDIM) and vertebral deformity index (VDIM) is based on vertebral height measurements of T4 through L5 and each measurement from T5 to L5 (anterior, middle and posterior height) is related to T4 and compared with the respective T4-related normal range. There was good agreement between the mean vertebral deformation from T5 to L4 graded by VDSG and VDIM, with correlation coefficients between R = 0.52 (p < 0.0001) and R = 0.9 (p < 0.0001) respectively. Spinal deformation at baseline as measured by SDIM and SDIG was correlated with R = 0.76 (p < 0.0001). For diagnosing a vertebra as fractured or not, VDIM reached a sensitivity of 82% and a specificity of 85% using VDSG as a standard, and on the other hand VDSG reached a sensitivity of 78% and a specificity of 88% in relation to VDIM. The changes in spinal deformation from week 0 to 150 were correlated with R = 0.58 (p < 0.0002) between SDIM and SDIG. To detect vertebral fracture progression the sensitivity of VDIM was 74% and the specificity 86%, when changes in VDSG were used as a standard.(ABSTRACT TRUNCATED AT 250 WORDS)

Distal metacarpal bone mineral density by dual energy X-ray absorptiometry (DEXA) scan. Methodological investigation and application in rheumatoid arthritis.

Dual energy X-ray absorptiometry scanning was performed along the axis of the third metacarpal bone of the non-dominant hand and including metacarpal bones 2, 3, 4 and 5. The Bone Mineral Density (BMD) was calculated for the distal 1/4 of each metacarpal bone. Ten patients with seropositive, erosive rheumatoid arthritis (RA) and 10 healthy, sex- and age-matched persons were investigated twice. The average BMD in RA patients was 73.6% of the value found in normals. The coefficient of variation on double determinations (in patients and controls) was 0.9-3.0%. We suggest that dual energy X-ray absorptiometry scanning with the scanning procedure proposed here may be an important instrument for the quantification of disease progression.

Acute effects of nasal salmon calcitonin on calcium and bone metabolism.

Effects of a single dose of 200 IU of nasal salmon calcitonin (SCT) on calcium metabolism and biochemical markers of bone turnover were investigated in 12 healthy male volunteers in a randomized, placebo-controlled, cross-over design. The nasal spray was given in the morning, and subsequently blood and urine samples were collected for 26 hours. There was a significant decrease in serum ionized calcium with a nadir 4 hours after administration of nasal SCT accompanied by a significant increase in serum parathyroid hormone (P = 0.01) and serum calcitriol (P = 0.04). Nasal SCT did not reduce urinary hydroxyproline/creatinine. Urinary deoxypyridinoline/creatinine was lowered significantly 2 hours after administration of nasal SCT and throughout the first 24 hours, but remained unchanged for the last 2 hours. On a 24-hour basis, urinary deoxypyridinoline/creatinine decreased from 14.1 (3.5) nmol/mmol to 11.7 (3.2) nmol/mmol after nasal SCT (P = 0.04). Nasal SCT did not change the serum levels of alkaline phosphatase, osteocalcin, and the carboxyterminal propeptide of type 1 procollagen. The results indicate that nasal SCT given as a single dose provokes a modest decrease in bone resorption lasting several hours, but leaves bone formation unaffected.

Lack of effect of nasal salmon calcitonin on cell-mediated immunity.

The calcium lowering hormone, calcitonin, also affects the immune system. The effect of nasal salmon calcitonin on lymphocyte transformation tests and on serum-ionised calcium was investigated in a randomised, double-blind and placebo-controlled study including 24 healthy adult volunteers. The participants received a single dose of either 200 IU of nasal salmon calcitonin or nasal placebo in the morning and measurements were done before and 3 h after administration of the spray. Nasal salmon calcitonin exerted a significant hypocalcemic effect, but did not interfere with antigen- or mitogen-induced expansion of T-lymphocytes. It is unlikely that nasal salmon calcitonin affects cell-mediated immunity in healthy subjects.

Changes in bone histomorphometry after long-term treatment with intermittent, cyclic etidronate for postmenopausal osteoporosis.

Intermittent, cyclic etidronate therapy (400 mg/day for 2 weeks followed by 13 weeks free from study drug administration) resulted in a significant increase in lumbar bone mineral content and a significant decrease in the rate of new vertebral fractures in patients with postmenopausal osteoporosis. To investigate the effect of the treatment on bone histomorphometry, transiliac crest bone biopsy samples were obtained in this study before treatment and after 60 and 150 weeks of treatment with either intermittent, cyclic etidronate (n = 33) or placebo (n = 33). After 60 weeks of etidronate therapy, significant decreases in activation frequency (from 0.55 to 0.09 year,-1 P < 0.01) and resorption depth (from 53.2 to 37.8 microns, P < 0.05) were observed, leading to a positive balance per remodeling cycle. In the placebo group, no significant changes were seen. The 150 week bone biopsy samples were suboptimal for analysis, probably as a result of a regional acceleratory phenomenon. Our results suggest that, as a result of reductions in both activation frequency and resorption depth, intermittent, cyclic etidronate therapy may protect the trabecular network against fortuitous perforations and thereby maintain the strength of the bony tissue.

Quantitation of urinary hydroxypyridinium cross-links from collagen by high-performance liquid chromatography.

Pyridinoline and deoxypyridinoline are intermolecular cross-links in mature collagen in bone and cartilage. The urinary excretion of the two compounds correlates well to bone turnover. A fast, sensitive, and accurate isocratic ion-pairing reverse-phase high-performance liquid chromatography method for measurement of pyridinoline and deoxypyridinoline in urine has been established. Intra- and inter-assay precision were 5-7% and 12-14%, respectively. Recovery for pyridinoline was 97.4% and for deoxypyridinoline 94.3%. The detection limit was 0.4 pmol. Pyridinoline:creatinine and deoxypyridinoline: creatinine ratios in healthy subjects, were 38.8 nmol:mmol and 13.0 nmol:mmol, respectively. Increased values of both cross-links were observed in children, in the age group 20-29 in both sexes, and in post-menopausal women.

Atrial natriuretic peptide (ANP) in chronic obstructive pulmonary disease (COPD): the relationship between plasma ANP and lung function. Effects of exercise and of the calcium antagonist, isradipine, on plasma ANP. A randomised, double-blind, placebo-controlled study.

In patients with severe chronic obstructive pulmonary disease (COPD) an increased pulmonary arterial pressure (PAP), a raised plasma level of atrial natriuretic peptide (ANP) and a correlation between increasing PAP and increasing plasma ANP have been shown. Furthermore, a negative correlation between lung function and PAP has been reported, and calcium antagonists have been claimed to decrease PAP. The purpose of the present study was to investigate whether 1) a negative correlation between lung function and plasma ANP could be demonstrated, whether 2) plasma ANP would increase during exercise in patients with COPD, and whether (3), in a randomised, placebo-controlled, double-blind design, a calcium antagonist was able to decrease plasma ANP at rest and modify the expected increase in plasma ANP during exercise. Eighteen patients with severe COPD were investigated. Plasma ANP was measured at rest and during exercise before and two hours after ingestion of either a single dose of 5 mg of isradipine, or a single dose of placebo. At rest, a correlation between lung function (forced vital capacity) and plasma ANP was found (rho = -0.49, P = 0.05). During the first exercise period, before ingestion of isradipine or placebo, the median level of ANP increased from 74 pg/ml at rest to 97 pg/ml at exhaustion (P less than 0.0002) (all patients). Administration of isradipine did not alter resting levels or exercise induced increases in plasma ANP. It is concluded, that in patients with severe COPD plasma ANP tends to be higher the more severely FVC is reduced. Plasma ANP increases during exercise. The calcium antagonist, isradipine, does not alter resting levels or exercise induced levels of plasma ANP.

Circulating levels of calciotropic hormones during treatment with nasal salmon calcitonin.

Circulating levels of calciotropic hormones were measured during one year of treatment with either 200 IU of salmon calcitonin daily or placebo as a nasal spray in 20 postmenopausal women with a former Colles' fracture. A supplement of 0.5 gram elemental calcium was given to all participants. Serum levels of parathyroid hormone and human calcitonin were determined with radioimmunoassays, and serum levels of vitamin D metabolites were determined with protein binding assays. We did not find any significant differences between the two groups with respect to serum levels of calciotropic hormones. In the salmon calcitonin treated group there was a tendency towards a small decrease in serum levels of human calcitonin and an increase in serum levels of calcitriol. Our results suggest that treatment with 200 IU of salmon calcitonin daily as a nasal spray does not markedly affect fasting serum levels of parathyroid hormone, human calcitonin, and vitamin D metabolites.

Bone disorder in men with chronic alcoholism: a reversible disease?

Disturbances in bone metabolism and histology have been recognized in chronic alcoholism. It has not been established whether they are reversible and the cause remains unclear. We studied various serum and urine variables (including serum PTH, calcium, D-vitamins, and osteocalcin concentrations), bone mineral content, and bone histomorphometrics in men who at present abused alcohol and compared the results to those from men who previously had abused alcohol but who had abstained from alcohol for at least 2 yr and from normal men. No significant differences were found in bone mineral content at the two measuring sites (distal forearm, lumbar spine) between drinkers, abstainers, and controls though a considerable proportion of both current drinkers and abstainers had subnormal values. Bone formation rate and turnover (expressed by the activation frequency) was significantly reduced in the current drinkers who also had lower serum PTH, 1,25-dihydroxycholecalciferol, and osteocalcin concentrations. Men who had abstained from alcohol consumption for at least 2 yr had results similar to those from normal men, suggesting that the disturbances in bone metabolism in men abusing alcohol are reversible. The decrease in bone turnover in the drinkers may be explained by the observed reduction in plasma PTH concentration or a direct toxic effect of ethanol on bone tissue leading to a deficient recruitment of osteogenic cells.