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Biomedical subjects

M Kleerekoper

Publications and source records attributed to M Kleerekoper.

At least 91 records · Page 5Linked to original sources
PubMed1987

Incidence of hip fractures in osteoporotic women treated with sodium fluoride.

It has been suggested recently that, although fluoride therapy may decrease the occurrence of vertebral fractures, it could increase the risk of hip fractures. To evaluate this possibility, we combined retrospective data from five medical centers that have had a large experience with this therapeutic regimen. In 416 osteoporotic patients who were followed for more than 1,000 patient-years of fluoride treatment, there were 17 nontraumatic hip fractures. This incidence of 1.6% per year is similar to the incidence, 1.9% per year, for 120 of the patients in this series who had been followed prospectively for 3 years prior to initiation of fluoride therapy. The expected incidence for women of the same age in the general community is 0.5% per year. Thus, untreated osteoporotic women are at increased risk for hip fracture, but treatment with fluoride seems neither to decrease nor to increase the incidence of hip fracture substantially.

Aged↗
PubMed1987

Hypophosphatemic osteomalacia and adult Fanconi syndrome due to light-chain nephropathy. Another form of oncogenous osteomalacia.

Two patients, one with myeloma (Patient 1) and the other with probable chronic lymphocytic leukemia (Patient 2), had reduced renal tubular phosphate reabsorption in the absence of hyperparathyroidism together with other features of the Fanconi syndrome, as consequences of the nephropathy associated with light-chain proteinuria. Both patients had hypophosphatemic osteomalacia, demonstrated for the first time in this condition by iliac bone histomorphometry after in vivo double tetracycline labeling, despite absence of bone pain or Looser zones. Neither patient was vitamin D-depleted, but plasma calcitriol level was normal in Patient 1 and low in Patient 2; only the latter patient had severe muscle weakness. Complete histologic correction of osteomalacia was achieved by treatment in accordance with the biochemical defects--oral phosphate therapy alone in Patient 1 and combined with calcitriol in Patient 2. Both patients are now symptom-free, five and three years after the initial diagnosis of bone disease and hematogenous malignancy. Thirteen previous instances of the same form of osteomalacia were reviewed; in most cases, the Fanconi syndrome developed before its probable cause became apparent. The Fanconi syndrome has also been reported in two cases of osteomalacia due to mesenchymal tumor, but not in osteomalacia associated with prostatic carcinoma. Light-chain nephropathy and consequent renal tubular dysfunction appears to be a third form of oncogenous osteomalacia.

Aged↗
PubMed1987

Atypical insufficiency fractures confused with Looser zones of osteomalacia.

Six women, aged 24-67 years, had osteopenia and insufficiency fractures, which suggested a diagnosis of osteomalacia. The insufficiency fractures occurred at traditional sites for Looser zones, were multiple in number, were symmetrically distributed in three patients, and did not heal promptly. Bone mass was low, as assessed by single-energy photon absorptiometry at the midshaft of the radius. Two postmenopausal women had vertebral compression fractures. Biochemical indices and bone histomorphometric analysis excluded osteomalacia, and in vivo double tetracycline labeling in five patients revealed both high and low bone turnover states. We propose more stringent radiographic criteria for the designation of the term "Looser zone" that retains the customary association between the radiologic event and osteomalacia. This paper also outlines a diagnostic strategy for future cases of atypical insufficiency fractures and proposes reasons for their resemblance to true Looser zones.

Adult↗
PubMed1987

Bone histomorphometry in hypogonadal and eugonadal men with spinal osteoporosis.

We present iliac bone histomorphometric data after in vivo double tetracycline labeling and related biochemical data from 14 nonalcoholic men referred for evaluation of symptomatic spinal osteoporosis. Six patients had previously undiagnosed hypogonadism, and 8 had normal gonadal function and no evident etiology for osteoporosis. Bone histomorphometry revealed no differences in structural measurements or resorption indices between the 2 groups. However, compared to reference values for normal postmenopausal women, osteoblast surface, mineralizing surface, and formation rate were normal or modestly increased in the hypogonadal men and significantly reduced in the idiopathic group. There were significant corresponding differences between the 2 groups in the fasting urinary hydroxyproline to creatinine ratio, an index of bone resorption, and serum total alkaline phosphatase, an index of bone formation. Plasma 25-hydroxyvitamin D levels did not differ between the 2 groups and were above 10 ng/mL in all patients. Plasma 1,25-dihydroxyvitamin D [1,25-(OH)2D] levels were normal in the hypogonadal group and significantly reduced in the idiopathic group, but did not correlate with any histological measurements. The formation indices fell substantially in 3 of 4 hypogonadal men after 7-14 months of therapy with testosterone and a calcium supplement. We conclude the following. In vitamin D-replete hypogonadal men with osteoporosis, 1,25-(OH)2D synthesis is normal, and bone remodeling is modestly increased and correctable by hormone replacement therapy, as in normal postmenopausal women. In middle-aged men with idiopathic osteoporosis, there is impairment of 1,25-(OH)2D synthesis and of the recruitment and activity of teams of osteoblasts, as in postmenopausal osteoporosis.

Adult↗
PubMed1987

Disseminated migratory osteoporosis: an unusual pattern of osteoporosis.

Regional migratory osteoporosis (RMO) is a well-defined clinical entity, consisting of migratory osteoporosis involving the lower extremities with associated radiographic changes. Idiopathic osteoporosis (IO) is considered to be a separate and distinct entity, occurring in young adults and consisting of axial osteoporosis and back pain. We describe a patient who had hybrid characteristics, both clinically and radiographically, and include iliac-crest biopsy histologic correlation. We believe that this pattern of osteoporosis in many ways resembles RMO, but with severe axial involvement; hence the term disseminated migratory osteoporosis.

Adult↗
PubMed1987

Vitamin D deficiency rickets. A report on three cases.

A resurgence of classic vitamin D deficiency rickets has been noted in the recent pediatric literature, but no mention of it appears in recent orthopedic journals. Three cases of vitamin D deficiency rickets occurred in children whose ages ranged from 14 to 17 months. Similar to the experience of others, all three occurrences were in young black children who were sustained on breast milk for prolonged periods (9-17 months). Differing from other cases in the recent literature, the patients' families were not consuming vitamin D deficient diets to comply with religious beliefs. Simple treatment with vitamin D supplementation was effective once the diagnosis was established.

Ankle↗
PubMed1986

Nonsecretory multiple myeloma with osteoporosis: immunocytologic and bone resorptive studies.

Two patients, ultimately found to have advanced nonsecretory multiple myeloma, presented with skeletal pain, diffuse skeletal demineralization, and fractures. The correct diagnosis was initially obscured by the absence of typical hematologic findings and discrete lytic bone lesions. Bone marrow examination was diagnostic. Intracytoplasmic IgA or IgD kappa was demonstrated in the myeloma cells of each case. Decreased quantitative polyclonal serum immunoglobulins and hypercalcemia were important clinical clues. The demonstration of increased osteoclast activating factor (OAF) derived from the cultured myeloma cells from each case suggests that the secretion of OAF and immunoglobulin are unrelated.

Bone Resorption↗
PubMed1986

Blood pressure response to changes in serum ionized calcium during hemodialysis.

The effect of an increasing serum ionized calcium concentration on blood pressure during hemodialysis was studied in a prospective cross-over trial. Twelve patients were dialyzed three times with a dialysate Ca concentration of 5.5 mg/dL and three times with one of 7.5 mg/dL. Dialysis with the high Ca dialysate was associated with less fall in the mean arterial pressure (p less than 0.001). No statistically significant changes occurred in serum osmolality, body weight, or heart rate after dialysis at the two dialysate Ca levels. Increasing the Ca concentration in dialysate may protect against intradialytic hypotension in some patients.

Adult↗
PubMed1986

Symptomatic osteoporosis in a man with hyperprolactinemic hypogonadism.

A 66-year-old man presented with height loss, back pain due to an L4 vertebral compression deformity, and marked osteopenia shown by radial photon absorptiometry. The patient had small testes and a long history of infertility and impotence. Plasma testosterone was low (130 ng/dL; normal, 300 to 1000 ng/dL) with marked elevation of serum prolactin (590 ng/mL; normal, 0 to 15 ng/mL). High-resolution computed tomography showed an invasive pituitary macroadenoma with a secondary empty sella turcica. Bone histomorphometry showed low-normal trabecular bone volume with normal formation and resorption indices. The patient was treated with calcium carbonate supplements, testosterone replacement, and bromocriptine mesylate without subsequent progression of the osteoporosis. This first report of hyperprolactinemic hypogonadism in a man who presented with overt osteoporosis shows the importance of evaluating gonadal function in all osteoporotic men.

Aged↗
PubMed1986

Reduced phosphate reabsorption unrelated to parathyroid hormone after renal transplantation: implications for the pathogenesis of hyperparathyroidism in chronic renal failure.

We measured nephrogenous cyclic adenosine monophosphate (NcAMP) excretion, an in vivo bioassay for endogenous parathyroid hormone (PTH) secretion, and renal phosphate threshold (TmP/GFR) in 33 renal allograft recipients with stable renal function (creatinine clearance greater than or equal to 60 ml/min/1.73 m2 body surface area, 6 months or more post-transplant) and in 9 kidney donors. Sixteen patients had normal parathyroid function, 8 had hypercalcemic hyperparathyroidism and 9 had normocalcemic hyperparathyroidism; the latter were apparently resistant to the hypercalcemic actions of endogenous PTH, but the cause for this was not apparent. In all four subject groups, TmP/GFR was significantly and similarly lower (by 0.8-1.0 mg/dl) than predicted by multiple regression on age, sex, corrected plasma calcium and NcAMP (determined in 306 subjects spanning a wide range of parathyroid function) indicating a major PTH-independent mechanism for reducing phosphate reabsorption in the presence of a single kidney. In all four groups the contribution of this mechanism to the observed depression of TmP/GFR was substantially greater than the contribution of increased PTH secretion. In all groups, but more so in the recipients than in the donors, fasting urinary phosphate excretion/GFR was increased, so that fasting plasma phosphate, although reduced, did not accurately reflect the severity of the defect in phosphate reabsorption. We conclude that the dominant mechanism for the adaptive decrease in renal tubular phosphate transport in response to nephron reduction does not require the participation of PTH and is manifest in the presence of fasting hypophosphatemia.

Absorption↗
PubMed1985

The role of three-dimensional trabecular microstructure in the pathogenesis of vertebral compression fractures.

We compared indices of three-dimensional microstructure of iliac trabecular bone between 26 patients with vertebral compression fractures due to postmenopausal osteoporosis and 24 control subjects without vertebral fracture, who were matched for age, sex, race, menopausal status, and several densitometric and histologic indices of both cortical and trabecular bone mass. The patients with fracture had a significantly lower mean value (1.03 +/- 0.15 vs. 1.26 +/- 0.26; P less than 0.005) for indirectly calculated mean trabecular plate density, an index of the number and connectivity of structural elements, and as a necessary corollary, a significantly higher mean value for the mean thickness of structural elements. Plate density was more than one standard deviation below the age-adjusted mean value for normal postmenopausal white females in 19 (73%) of the fracture cases and in only 5 (21%) of the nonfracture cases (P less than 0.001). We conclude that the biomechanical competence of trabecular bone is dependent not only on the absolute amount of bone present but also on the trabecular microstructure.

Aged↗
PubMed1985

Irreversible bone loss in osteomalacia. Comparison of radial photon absorptiometry with iliac bone histomorphometry during treatment.

We examined the relationships between the changes in bone mineral deficit in the radius, determined by single-energy photon absorptiometry at standard proximal and distal sites, and in the ilium, determined by bone histomorphometry, during the treatment of osteomalacia of diverse etiology in 28 patients. In the ilium, relative osteoid volume decreased by 75-80% in both cortical bone (from 6.0% to 1.5%) and trabecular bone (from 30.1% to 6.6%) during a mean treatment duration of 2 yr. There was also a significant fall in iliac cortical porosity from 10.3% to 7.8%. As a result, mineralized bone volume increased by 7.5% in cortical and by 40.1% in trabecular bone; the cortical and trabecular increments were correlated (r = 0.69, P less than 0.001). The properly weighted increase for the entire tissue sample was 18.6%. By contrast, there was no change in bone mineral at either radial site, although there was a 2% increase at both sites when allowance was made for age-related bone loss during treatment. The proximal and distal age-adjusted increments was correlated (r = 0.76, P less than 0.001), but there was no correlation between the changes in any photon absorptiometric and any histomorphometric index. In that iliac cortical bone turnover in normal subjects was 7.2%/yr, we estimated the rate of bone turnover to be less than 2%/yr at both proximal and distal radial sites, including any trabecular bone present at the distal site. Compared to appropriate control subjects, the bone mineral deficits fell during treatment from 19.2% to 17.1% at the proximal radius (greater than 95% cortical bone) and from 20.5% to 18.5% at the distal radius (greater than 75% cortical bone). In the ilium the deficits, assuming attainment of normal values for osteoid volume and cortical porosity, fell from 41.7% to 36.1% in cortical and from 31.5% to 6.3% in trabecular bone, the properly weighted combined deficit falling from 38.6% to 27.7%. The irreversible iliac cortical deficit was entirely due to cortical thinning because of increased net endosteal resorption; the resultant expansion of the marrow cavity offset the modest loss of fractional trabecular mineralized bone. We conclude: in osteomalacia there is a large irreversible and a small reversible bone mineral deficit at both proximal and distal radial sites, in similar proportion to the iliac cortex but of smaller magnitude; the anatomic basis of the irreversible bone mineral deficit at all three sites that persists despite correction of the mineralization defect by appropriate treatment is thinning of cortical bone, most likely owing to prolonged secondary hyperparathyroidism; (c) there is no evidence that the proportion of trabecular bone in the distal radius at any site proximal to the radioulnar joint has any relevance to the interpretation of measurements made at that site; (d) there are at least three functional subdivisions of trabecular bone depending on proximity to hematopoietic marrow, fatty marrow, or synovium; and (e) single photon absorptiometry of the radius is an excellent method for measuring cortical bone mass in the appendicular skeleton, but is of little value for the assessment of changes in trabecular bone status.

Biopsy↗
PubMed1985

Dissociation between the effects of endogenous parathyroid hormone on adenosine 3',5'-monophosphate generation and phosphate reabsorption in hypocalcemia due to vitamin D depletion: an acquired disorder resembling pseudohypoparathyroidism type II.

In 6 of 8 adults with severe hypocalcemia and osteomalacia due to vitamin D depletion, basal excretion of nephrogenous cAMP (NcAMP) was increased, but the mean renal phosphate threshold (TmP/GFR) was normal, indicating that the steady state phosphaturic response to cAMP generated by endogenous PTH was impaired, as in pseudohypoparathyroidism type II. In all 6 patients, correction of hypocalcemia by administration of vitamin D and calcium restored the normal relationship between NcAMP and TmP/GFR. By contrast, in 13 patients with normocalcemic osteomalacia due to vitamin D depletion, TmP/GFR was reduced, with a significant negative regression on NcAMP, and rose to normal after treatment. Bone histomorphometry after double tetracycline labeling did not differ significantly between the 2 groups. In 72 patients with primary hyperparathyroidism, the slope of the negative regression of TmP/GFR on NcAMP was the same as in normocalcemic secondary hyperparathyroidism, but the adjusted mean for TmP/GFR was significantly lower. We conclude that the effect of endogenous PTH on phosphate reabsorption varies with the level of plasma calcium, and that dissociation between this effect and the generation of cAMP is nonspecific and can be a consequence of hypocalcemia. Exclusion of vitamin D depletion should be an additional diagnostic criterion for pseudohypoparathyroidism type II.

Adult↗
PubMed1983

Relationships between surface, volume, and thickness of iliac trabecular bone in aging and in osteoporosis. Implications for the microanatomic and cellular mechanisms of bone loss.

We devised a new method for examining the structural changes that occur in trabecular bone in aging and in osteoporosis. With simultaneous measurement of total perimeter and bone area in thin sections, indirect indices of mean trabecular plate thickness (MTPT) and mean trabecular plate density (MTPD) can be derived, such that trabecular bone volume = MTPD X MTPT. MTPD is an index of the probability that a scanning or test line will intersect a structural element of bone, and is the reciprocal of the mean distance between the midpoints of structural elements, multiplied by pi/2. We applied this method to iliac bone samples from 78 normal subjects, 100 patients with vertebral fracture, and 50 patients with hip fracture. The reduction in trabecular bone volume observed in normal subjects with increasing age was mainly due to a reduction in plate density, with no significant decrease in plate thickness. The further reduction in trabecular bone volume observed in patients with osteoporotic vertebral fracture was mainly due to a further reduction in plate density. There was a relatively smaller reduction in plate thickness that was statistically significant in males but not in females. Only in patients with hip fracture did trabecular thinning contribute substantially to the additional loss of trabecular bone in osteoporosis relative to age. These data indicate that age-related bone loss occurs principally by a process that removes entire structural elements of bone; those that remain are more widely separated and some may undergo compensatory thickening, but most slowly become reduced in thickness. We propose that the process of removal is initiated by increased depth of osteoclastic resorption cavities which leads to focal perforation of trabecular plates; this is followed by progressive enlargement of the perforations with conversion of plates to rods. The resulting structural changes are more severe in osteoporotic patients than in normal subjects, but have been completed in most patients before they develop symptoms.

Adolescent↗